N-phenylarylsulfonamide compound, pharmaceutical composition comprising the compound as active ingredient, synthetic intermediate for the compound and process for it&#39;s preparation

ABSTRACT

An N-phenylarylsulfonylamide compound of formula (I) 
     
       
         
         
             
             
         
       
     
     (R 1  is COOH etc.; R 2  is hydrogen, methyl, etc.; R 3  and R 4  are a combination of methyl and methyl, etc.; R 5  is isopropyl etc.; Ar is thiazolyl, pyridyl, 5-methyl-2-furyl each optionally substituted with methyl; n is zero or 1), a synthetic intermediate for the compound and a process for its preparation. The compound of formula (I) binds to a prostaglandin E 2  receptor, especially an EP 1  subtype receptor, and antagonizes it. It is less affected by protein binding, so it has a satisfactory in vivo activity. Therefore, it is considered to be useful as an analgesic, an antipyretic agent, an agent for the treatment of pollakiuria (frequent urination) and/or lower urinary tract disease syndrome or an antineoplastic agent.

TECHNICAL FIELD

The present invention relates to an N-phenylarylsulfonamide compound.

More detailed, the present invention relates to

(1) an N-phenylarylsulfonamide compound of formula (I)

wherein all symbols have the same meanings as defined hereinafter,(2) a prostaglandin E₂ receptor (EP₁) antagonist which comprises thecompound as an active ingredient,(3) a compound of formula (II)

wherein all symbols have the same meanings as defined hereinafter, and(4) a process for its preparation.

BACKGROUND ART

Prostaglandin E₂ (abbreviated as PGE₂) has been known as a metabolite inthe arachidonate cascade. It has also been known that PGE₂ possesses acyto-protective activity, a uterine contractive activity, apain-inducing effect, a promoting effect on digestive peristalsis, anawakening effect, a suppressive effect on gastric acid secretion, ahypotensive effect, a diuretic activity and so on.

In a recent study, it was found that a PGE₂ receptor is divided intosome subtypes which possess different physical roles from each other. Atpresent, four receptor subtypes are known and they are called EP₁, EP₂,EP₃ and EP₄ respectively (Negishi M. et al., J. Lipid Mediators CellSignaling, 12, 379-391 (1995)).

PGE₂ possesses a variety of physiological activities, so the undesiredaction other than the aimed one is shown as side effect. The researchfor the role of each receptor subtype and the investigation of thecompound which only shows the effect on the specific subtype have beencarried out to overcome such a problem.

Among these subtypes, it has been known that EP₁ subtype relates toinduction pain, pyrexia (induction fever) and diuresis (ref Br. J.Pharmacol., 112, 735-740 (1994); European J. Pharmacol., 152 273-279(1988); Gen Pharmacol., September 1992, 23(5) 805-809). Therefore,compounds which antagonize this receptor are considered to be useful asanalgesics, as antipyretic agents and as agents for treating pollakiuria(frequent urination).

It has also been known that EP₁ antagonists possess a suppressive effecton aberrantcryptfoci and formation of intestinal polyps, and that theyindicate an effective anti-tumor activity (ref. WO00/69465).

After drugs are absorbed in the body, they mainly migrate into thebloodstream. Then they are transported in the blood and are delivered totarget organs. Finally they exert their potency. However, some drugs donot exert their potency because they combine with some proteins, whichis contained in blood as nutritive substances. While some compounds areeffective in in vitro experiment, it may often turn out that they arenot effective in in vivo experiment. And it has been well known thatthere is not a specific structure-activity relationship on bindingbetween drugs and proteins, and that it is very difficult to find outthe ordinality.

The present inventors found a useful compound which is an EP₁antagonist, and filed a patent application. In the specification ofWO98/27053 (EP947500), it is disclosed that a sulfonamide compound offormula (A)

wherein the group

are each independently C5-15 carbocyclic ring etc.; Z^(1A) is —COR¹etc.; Z^(2A) is hydrogen etc.; R^(1A) is hydroxy etc.; Z^(3A) is singlebond etc.; Z^(4A) is SO₂ etc.; Z^(5A) is 5 to 7 membered heterocyclicring containing one or two oxygen, sulfur or nitrogen atom(s), which maybe substituted with 1 to 5 R^(5A) etc.; R^(5A) (if two or more R^(5A),each independently) is hydrogen, C1-6 alkyl etc.; R^(2A) is Z^(7A)-C1-4alkylene etc.; Z^(7A) is oxygen etc.; R^(3A) is trifluoromethyl etc.;R^(4A) is C1-8 alkyl etc.; n^(A) and t^(A) are each independently 1 to 4(as excerpt),binds to a PGE₂ receptor, especially the EP₁ receptor, to show anagonistic or an antagonistic activity. The specification disclosed thatthe compound having the antagonistic activity is useful for theprevention of abortion, as an analgesic, as an antidiarrhoic, as ahypnagogic agent and for treating pollakiuria (frequent urination),while the one having an agonistic activity is useful for abortion, as anabstergent, as an antiulcer agent, as an antigastritis agent, as anantihypertensive agent, as a diuretic agent.

In this patent application, for example, the following compounds aredisclosed specifically.

(1) Example 18(93)

(2) Example 18(113)

(3) Example 18(125)

(4) Example 18(121)

(5) Example 18(126)

(6) Example 18(59)

(7) Example 18(124)

(8) Example 18(94)

(9) Example 21(13)

(10) Example 21(14)

In the process of the researches about these compounds, it was revealedthat these compounds have some problems that they are susceptible to theinfluence of protein binding and that they do not have a satisfactory invivo activity.

DISCLOSURE OF THE INVENTION

As a result of an energetic investigation to find those compounds whichselectively bind to EP₁ subtype receptor and have a satisfactory in vivoactivity owing to being less affected by protein binding, the presentinventors have found that the only N-phenylarylsulfonamide compound offormula (I) has a very strong in vivo activity and completed the presentinvention.

The present inventors have also found that a novel intermediate offormula (II)

wherein all symbols have the same meanings as defined hereinafter, whichis used for the preparation of the compound of formula (I) and a methodfor the preparation thereof.

Various compounds are disclosed in the specification of WO 98/27053, asreferred to above, but no compounds of the present invention aredisclosed, and there are neither description nor suggestion as to aboveproblems nor methods for the resolution.

The present invention relates to

(1) an N-phenylarylsulfonylamide compound of formula (I)

wherein R¹ is COOH, 5-tetrazolyl, 5-oxo-1,2,4-oxadiazolyl, CH₂OH or5-oxo-1,2,4-thiadiazolyl;

R² is hydrogen, methyl, methoxy or chloro;

R³ and R⁴ are a combination of (1) methyl and methyl, (2) methyl andchloro, (3) chloro and methyl or (4) trifluoromethyl and hydrogen, or R³and R⁴ are taken together with the carbons to which R³ and R⁴ areattached to form (5) cyclopentene, (6) cyclohexene or (7) benzene ring;

R⁵ is isopropyl, isobutyl, 2-methyl-2-propenyl, cyclopropylmethyl,methyl, ethyl, propyl or 2-hydroxy-2-methylpropyl;

Ar is thiazolyl optionally substituted with methyl, pyridyl or5-methyl-2-furyl; and

n is zero or 1, and when R¹ is 5-tetrazolyl, 5-oxo-1,2,4-oxadiazolyl or5-oxo-1,2,4-thiazolyl, n is zero,

an ester thereof or a non-toxic salt thereof,

(2) a method for the preparation thereof,(3) an antagonist of PGE₂ receptor, EP₁ subtype receptor, comprising itas an active ingredient,(4) a compound of formula (II)

wherein Ar′ is an optionally substituted 5 to 10 membered heterocyclicring and R⁶ is

which is an intermediate for the compound of formula (I), and(5) a method for the preparation of the compound of formula (II).

The present inventors synthesized almost all combinations of thecompounds of formula (I) of the present invention, and confirmed theiractivities. And all compounds thereof are preferable.

More preferable compound(s) have or has Ar of 5-methyl-2-furyl,2-thiazolyl, 5-methyl-2-thiazolyl, 2-pyridyl and 3-pyridyl.

Specifically, preferable compounds are:

-   4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamic    acid,-   4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoic    acid,-   4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoic    acid,-   4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoic    acid,-   4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoic    acid,-   3-chloro-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoic    acid,-   3-chloro-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoic    acid,-   3-methoxy-4-[2-[N-isopropyl-N-(5-methyl-2-furyl    sulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoic acid,-   3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   3-methoxy-4-[2-[N-isopropyl-N-(5-methyl-2-furyl    sulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic acid,-   3-methoxy-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   3-methoxy-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoic    acid,-   3-chloro-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   3-chloro-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]cinnamic    acid,-   4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamic    acid,-   4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamic    acid,-   4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic    acid,-   3-methyl-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamic    acid,-   3-methyl-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   3-methyl-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic    acid,-   4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic    acid,-   N-[4-chloro-5-methyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide,-   3-methoxy-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamic    acid,-   N-[4,5-dimethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide,-   N-[4,5-dimethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(5-methyl-2-furyl)sulfonylamide,-   N-[4-chloro-5-methyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide,-   N-[4-chloro-5-methyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-(5-methyl-2-furyl)sulfonylamide,-   N-[4-chloro-5-methyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide,-   4-[6-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   4-[6-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   4-[7-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-1,2,3,4-tetrahydronaphtharen-6-yloxymethyl]benzoic    acid,-   4-[7-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-1,2,3,4-tetrahydronaphtharen-6-yloxymethyl]benzoic    acid,-   N-[4,5-dimethyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-(5-methyl-2-furyl)sulfonylamide,-   N-[4,5-dimethyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide,-   N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(5-methyl-2-furyl)sulfonylamide,-   N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide,-   N-[4,5-dimethyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide,-   3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamic    acid,-   N-[4,5-dimethyl-2-[2-methoxy-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide,-   N-[4,5-dimethyl-2-[2-methoxy-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-(5-methyl-2-furyl)sulfonylamide,-   4-[6-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   3-methyl-4-[6-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   3-methyl-4-[6-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   4-[2-[N-(2-methyl-2-propenyl)-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   3-methyl-4-[6-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   3-methyl-4-[6-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   4-[6-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   4-[3-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-2-naphthyloxymethyl]benzoic    acid,-   3,5-dimethyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoic    acid,-   3-methyl-4-[6-[N-(2-methyl-2-propenyl)-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   4-[6-[N-cyclopropylmethyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]-3-methylbenzoic    acid,-   4-[6-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]-3-methylbenzylalcohol,-   3-methyl-4-[6-[N-methyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   4-[6-[N-ethyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]-3-methylbenzoic    acid,-   4-[6-[N-methyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   4-[6-[N-ethyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   4-[6-[N-propyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   4-[4,5-dimethyl-2-[N-(2-methyl-2-propenyl)-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]-3-methylbenzoic    acid,-   4-[6-[N-(2-methyl-2-propenyl)-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   4-[6-[N-cyclopropylmethyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   4-[6-[N-(2-propenyl)-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   3-methyl-4-[6-[N-propyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   3-methyl-4-[6-[N-(2-propenyl)-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   4-[4,5-dimethyl-2-[N-methyl-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]benzoic    acid,-   4-[4,5-dimethyl-2-[N-ethyl-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]benzoic    acid,-   4-[4,5-dimethyl-2-[N-(5-methyl-2-furylsulfonyl)-N-propylamino]phenoxymethyl]benzoic    acid,-   4-[3-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]-3-methylbenzoic    acid,-   4-[3-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]-3-methylbenzoic    acid,-   4-[3-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]cinnamic    acid,-   4-[3-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]cinnamic    acid,-   3-methyl-4-[3-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]cinnamic    acid,-   3-methyl-4-[3-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]cinnamic    acid,-   4-[4,5-dimethyl-2-[N-[(5-methyl-2-furyl)sulfonyl]-N-2-propenylamino]phenoxymethyl]benzoic    acid,-   4-[4,5-dimethyl-2-[N-methyl-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]-3-methylbenzoic    acid,-   4-[4,5-dimethyl-2-[N-ethyl-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]-3-methylbenzoic    acid,-   4-[4,5-dimethyl-2-[N-(5-methyl-2-furylsulfonyl)-N-propylamino]phenoxymethyl]-3-methylbenzoic    acid,-   4-[4,5-dimethyl-2-[N-(5-methyl-2-furylsulfonyl)-N-(2-propenyl)amino]phenoxymethyl]-3-methylbenzoic    acid,-   4-[4,5-dimethyl-2-[N-(2-hydroxy-2-methylpropyl)-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]-3-methylbenzoic    acid,-   4-[6-[N-(2-hydroxy-2-methylpropyl)-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]-3-methylbenzoic    acid,-   4-[4,5-dimethyl-2-[N-cyclopropylmethyl-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]benzoic    acid,-   4-[4,5-dimethyl-2-[N-(2-hydroxy-2-methylpropyl)-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]benzoic    acid,-   4-[6-[N-(2-hydroxy-2-methylpropyl)-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   4-[4,5-dimethyl-2-[N-cyclopropylmethyl-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]-3-methylbenzoic    acid,-   4-[2-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoic    acid,-   4-[2-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoic    acid,-   4-[2-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamic    acid,-   4-[2-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamic    acid,-   4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoic    acid,-   4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamic    acid,-   4-[2-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoic    acid,-   N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-thiazolylsulfonylamide,-   N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-2-thiazolylsulfonylamide,-   N-[4-trifluoromethyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-2-thiazolylsulfonylamide,-   N-[4-trifluoromethyl-2-[4-(5-oxo-1,2,4-thiadiazol-3-yl-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-2-thiazolylsulfonylamide,-   4-[2-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoic    acid,-   4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoic    acid,-   3-chloro-4-[2-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoic    acid,-   3-methoxy-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoic    acid,-   3-methoxy-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoic    acid,-   N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide,-   N-[4-trifluoromethyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide,-   N-[4-trifluoromethyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide,-   4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoic    acid,-   3-chloro-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoic    acid,-   3-methoxy-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoic    acid,-   N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide,-   3-methyl-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   3-methyl-4-[2-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   3-methoxy-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   3-chloro-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   3-chloro-4-[2-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   4-[2-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]cinnamic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamic    acid,-   3-chloro-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamic    acid,-   3-methyl-4-[2-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic    acid,-   4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]cinnamic    acid,-   N-[4-chloro-5-methyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide,-   N-[4-chloro-5-methyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide,-   4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic    acid,-   N-[4-trifluoromethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide,-   N-[4-trifluoromethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide,-   3-chloro-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic    acid,-   N-[4,5-dimethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide,-   N-[4,5-dimethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide,-   N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide,-   N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide,-   N-[4-chloro-5-methyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide,-   N-[4-chloro-5-methyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide,-   N-[4-chloro-5-methyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide,-   N-[4-chloro-5-methyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide,-   3-methoxy-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic    acid,-   N-[4,5-dimethyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide,-   N-[4,5-dimethyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide,-   N-[4,5-dimethyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide,-   N-[4,5-dimethyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide,-   N-[4,5-dimethyl-2-[2-methoxy-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide,-   N-[4,5-dimethyl-2-[2-methoxy-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide,-   4-[6-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   4-[6-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   3-methyl-4-[6-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   3-methyl-4-[6-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   3-methyl-4-[2-[N-(2-methyl-2-propenyl)-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoic    acid,-   4-[2-[N-(2-methyl-2-propenyl)-N-(4-methyl-2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamic    acid,-   3-methyl-4-[2-[N-(2-methyl-2-propenyl)-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   3-methyl-4-[6-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   3-methyl-4-[6-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   3-methyl-4-[6-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   4-[6-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   4-[6-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   4-[6-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   4-[6-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   3-methyl-4-[6-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   4-[2-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   4-[2-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   4-[2-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic    acid,-   4-[2-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic    acid,-   4-[6-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   4-[6-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   3-methyl-4-[2-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   3-methyl-4-[2-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic    acid,-   3-methyl-4-[6-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   3-methyl-4-[6-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   4-[3-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]naphthalen-2-yloxymethyl]benzoic    acid,-   4-[3-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]naphthalen-2-yloxymethyl]benzoic    acid,-   4-[3-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]naphthalen-2-yloxymethyl]-3-methylbenzoic    acid,-   4-[3-[N-isopropyl-N-[2-(4-methylthiazolyl)sulfonyl]amino]naphthalen-2-yloxymethyl]-3-methylbenzoic    acid,-   4-[3-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]naphthalen-2-yloxymethyl]cinnamic    acid,-   4-[3-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]naphthalen-2-yloxymethyl]cinnamic    acid,-   4-[4,5-dimethyl-2-[N-methyl-N-(4-methyl-2-thiazolylsulfonyl)amino]phenoxymethyl]-3-methylbenzoic    acid,-   4-[4,5-dimethyl-2-[N-ethyl-N-(4-methyl-2-thiazolylsulfonyl)amino]phenoxymethyl]-3-methylbenzoic    acid,-   4-[4,5-dimethyl-2-[N-propyl-N-(4-methyl-2-thiazolylsulfonyl)amino]phenoxymethyl]-3-methylbenzoic    acid,-   4-[4,5-dimethyl-2-[N-(2-propenyl)-N-(4-methyl-2-thiazolylsulfonyl)amino]phenoxymethyl]-3-methylbenzoic    acid,-   4-[4,5-dimethyl-2-[N-cyclopropylmethyl-N-(4-methyl-2-thiazolylsulfonyl)amino]phenoxymethyl]-3-methylbenzoic    acid,-   4-[4,5-dimethyl-2-[N-(2-hydroxy-2-methylpropyl)-N-(4-methyl-2-thiazolylsulfonyl)amino]phenoxymethyl]-3-methylbenzoic    acid,-   4-[6-[N-(2-methyl-2-propenyl)-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   4-[6-[N-(4-methyl-2-thiazolylsulfonyl)-N-(2-propenyl)amino]indan-5-yloxymethyl]benzoic    acid,-   4-[6-[N-cyclopropylmethyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   4-[3-[N-isobutyl-N-[2-(4-methylthiazolyl)sulfonyl]amino]naphthalen-2-yloxymethyl]-3-methylcinnamic    acid,-   4-[3-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]naphthalen-2-yloxymethyl]-3-methylbenzoic    acid,-   4-[6-[N-ethyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   4-[6-[N-(4-methyl-2-thiazolylsulfonyl)-N-propylamino]indan-5-yloxymethyl]benzoic    acid,-   4-[6-[N-methyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   3-methyl-4-[6-[N-methyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   4-[6-[N-ethyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]-3-methylcinnamic    acid,-   3-methyl-4-[6-[N-(2-methyl-2-propenyl)-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   4-[6-[N-cyclopropylmethyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]-3-methylcinnamic    acid,-   3-methyl-4-[6-[N-(4-methyl-2-thiazolylsulfonyl)-N-(2-propenyl)amino]indan-5-yloxymethyl]cinnamic    acid,-   4-[6-[N-(2-hydroxy-2-methylpropyl)-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]-3-methylcinnamic    acid,-   3-methyl-4-[6-[N-(4-methyl-2-thiazolylsulfonyl)-N-propylamino]indan-5-yloxymethyl]cinnamic    acid,-   4-[6-[N-(2-hydroxy-2-methylpropyl)-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoic    acid,-   4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamic    acid,-   4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoic    acid,-   3-chloro-4-[2-[N-isopropyl-N-(2-pyridylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoic    acid,-   N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-3-pyridylsulfonylamide,-   N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide,-   4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoic    acid,-   3-chloro-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamic    acid,-   3-methoxy-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   3-methoxy-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide,-   N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide,-   3-methyl-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoic    acid,-   4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic    acid,-   N-[4-trifluoromethyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide,-   4-[2-[N-isopropyl-N-(2-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic    acid,-   4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic    acid,-   3-methyl-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic    acid,-   N-[4-trifluoromethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide,-   3-chloro-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic    acid,-   N-[4,5-dimethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide,-   N-[4,5-dimethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide,-   N-[4-chloro-5-methyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide,-   N-[4,5-dimethyl-2-[2-chloro-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide,-   N-[4,5-dimethyl-2-[2-chloro-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-3-pyridylsulfonylamide,-   N-[4,5-dimethyl-2-[2-chloro-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide,-   3-methyl-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]cinnamic    acid,-   N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide,-   N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide,-   N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide,-   3-chloro-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamic    acid,-   N-[4-chloro-5-methyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide,-   N-[4-chloro-5-methyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide,-   N-[4,5-dimethyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide,-   N-[4,5-dimethyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide,-   N-[4,5-dimethyl-2-[2-methoxy-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide,-   N-[4,5-dimethyl-2-[2-methoxy-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide,-   N-[4,5-dimethyl-2-[2-methoxy-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide    and    N-[4,5-dimethyl-2-[2-methoxy-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide.

Esters:

Among the compounds of formula (I) of the present invention, thecompound of formula (I-B) may be converted into the corresponding esterby methods known per se. The conversion into ester is useful, because ofincrease of stability and absorbability of the compound. An alkyl esteris preferable. C1-4 alkyl ester is more preferable. The ester of formula(I-B) may be prepared by methods known per se. It may also be obtainedas the compound of formula (I-A) in the process of preparing thecompound in the present invention.

Salts:

The compound of formula (I) of the present invention may be convertedinto the corresponding salt by methods known per se. A non-toxic andwater-soluble salt is preferable. A suitable salt, for example, includesa salt of alkali metals (potassium, sodium, etc.), a salt of alkalineearth metals (calcium, magnesium, etc.), an ammonium salt, a salt ofpharmaceutically acceptable organic amines (tetramethylammonium,triethylamine, methylamine, dimethylamine, cyclopentylamine,benzylamine, phenethylamine, piperidine, monoethanolamine,diethanolamine, tris(hydroxymethyl)methylamine, lysine, arginine,N-methyl-D-glucamine, etc.).

Method for the Preparation of the Compound in the Present Invention:

The compound of formula (I) of the present invention may be prepared bymethods described in WO98/27053, or according to the reaction schemesoutlined below. Details of the process are described below.

In the schemes, R is C1-4 alkyl, Tf is trifluoromethanesulfonyl and theother symbols have the same meanings as defined hereinbefore.

-   R: C1-4 alkyl;-   Ms: mesyl;-   Tf₂O: trifluoromethanesulfonic acid anhydride;-   Et: ethyl;-   TCDI: 1,1′-thiocarbonyldiimidazole.

Among the compounds of formula (I), when Ar is a heterocyclic ringhaving a basic part, its corresponding sulfonyl halide (the compound offormula (VII)) described in the reaction scheme (A) is susceptible toheat, and it was found that it easily decomposed when it is left as itwas (see Comparison Example 1).

Particularly, it is easily expected that a sulfonyl halide having abasic part such as a heterocyclic ring containing a nitrogen atom iseasily decomposed, since sulfonyl halide compounds are generallyunstable to bases.

From these, in preparing a sulfonyl halide having a basic part, it wasconcerned that (1) it is hard to isolate a sulfonyl halide because theconcentrated sulfonyl halide is unstable after evaporation of thesolvent after the reaction terminated, and that (2) it was probable thatthe sulfonyl halide might decompose in the process of preparing asulfonamide from it, when subjected to temperature higher than ambienttemperature for a long time.

As described above, when the sulfonyl halide easily decomposes, it isdifficult to determine the actual quantity of the sulfonyl halide, andit is cumbersome to treat it. When the sulfonamide compound is preparedby subjecting to condensation reaction with an amine compound, low yieldis concerned due to the decomposition of the sulfonyl halide in theindustrial mass production.

As to the method for the preparation of a sulfonamide, condensationreaction with a sulfonyl halide and an amine is generally known.

They disclose a method for transforming a phenylsulfonyl chloride into asulfonamide or a sulfonic acid ester via an addition of an imidazole toa phenylsulfonyl chloride followed by N-methylation (J. Org. Chem., 57,4775-4777 (1992)), and it is described that the method is useful in thecase of reaction with a nucleophile having low nucleophilicity orsterically hindered one. However, it is not described nor suggested thatthe methods improve the stability of the sulfonyl halide.

The present inventors have investigated to convert a sulfonyl halidehaving a heterocyclic ring of formula (III) to a more stable compound tofind that the purpose was accomplished by converting it to the compoundsof formulae (II-A) and (II-B) according to the method for thepreparation as shown in the following reaction scheme (C).

In the reaction scheme (C), step (a) is a method of converting to astable sulfonyl compound with 1-hydroxybenzotriazole. For example, it iscarried out with 1-hydroxybenzotriazole, in an organic solvent (an ether(t-butyl methyl ether, diethyl ether, tetrahydrofuran, etc.), a halogensolvent (methylene chloride, chloroform, etc.), etc.) in the presence ofa base (triethylamine, diisopropylethylamine, dimethylaminopyridine,pyridine, etc.), at temperature of −20 to 30° C.

The step (b) is also a method for preparing a stable sulfonyl compound;for example, it is carried out in an organic solvent (an ether (t-butylmethyl ether, diethyl ether, tetrahydrofuran, etc.), a halogen solvent(methylene chloride, chloroform, etc.), etc.) with N-methylimidazole attemperature of −20 to 30° C.

The steps (a) and (b) are preferably carried out under an anhydrouscondition under the atmosphere of inert gas.

Particularly, when the compound of formula (III) is unstable to heat,the each step (a) and (b) may be carried out without concentrating theprepared sulfonyl halide solution.

Sulfonyl halide of formula (III) is obtained as a solution afterpreparation, and generally it can be isolated by concentration of thesolution. If the materials are exposed to high temperature whileconcentrating, there is a possibility that a sulfonyl halide maydecompose by heating in a large scale, while there is no problem inparticular in a small scale (see Comparison Example). Therefore, thetransforming into the compound of formulae (II-A) or (II-B) withoutconcentration of solution ensures a low degradability of a sulfonylchloride with its high reactivity (see Examples 7 and 8).

In the reaction scheme, the sulfonyl halide of formula (III) used as astarting material is known in itself or may be prepared easily in aconventional method from a known compound. The other starting materialsand reagents in the present invention are known in themselves or may beprepared according to conventional methods.

The reaction scheme (C) can provide a method for the preparation of thecompound of formula (VIII), wherein Ar is a basic heterocyclic ring. Themethod of the present invention is useful for stabilization of not onlyan unstable intermediate of the compound of formula (I) but also anunstable sulfonyl chloride with a basic heterocyclic ring.

In the present invention, 5 to 10 membered heterocyclic ring representedby Ar′ is, 5 to 10 membered heterocyclic ring comprising 1 to 4 ofnitrogen atom(s), 1 to 2 of oxygen atom(s) and/or 1 of sulfur atom;specifically, it represents a basic heterocyclic ring such as thiazole,isothiazole, isoxazole, pyrazine, pyrimidine, pyridazine, pyridine,pyrrole, imidazole, pyrazole, triazole, indole, indoline, purine,quinoline, isoquinoline, phthalazine, naphthyridine, quinoxaline,cinnoline, pyrrolidine, pyrroline, imidazolidine, imidazoline,pyrazoline, etc.

In the present invention, Ar′ may be substituted with 1 to 4 of C1-8alkyl, C1-8 alkoxy, halogen atom, cyano, nitro, C2-8 acyl, dialkylamino,monoalkylamino, monoalkylaminocarbonyl, dialkylaminocarbonyl, C5-10carbocyclic ring or 5 to 10 membered heterocyclic ring.

In the present invention, C1-8 alkyl as a substituent of Ar′ is, methyl,ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl or isomers thereof.

In the present invention, C1-8 alkoxy is methoxy, ethoxy, propoxy,butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy or isomers thereof.

In the present invention, halogen atom as a substituent of Ar′ is,fluorine, chlorine, bromine or iodine atom.

In the present invention, C3-10 carbocyclic ring as a substituent of Ar′is, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane,cyclopentene, cyclohexene, cyclopentadiene, cyclohexadiene, benzene,pentalene, indene, naphthalene, biphenylene, perhydropentalene,perhydroindene, perhydronaphthalene ring, etc.

In the present invention, 5 to 10 membered heterocyclic ring as asubstituent of Ar′ is, 5 to 10 membered mono- or bi-heterocyclic ringcontaining 1 to 4 nitrogen atom(s), 1 to 2 oxygen atom(s) and/or 1sulfur atom, including 5 to 10 membered mono- or bi-heterocyclic aryl,or partially or fully saturated ring thereof.

In the present invention, 5 to 10 membered mono- or bi-heterocyclic arylcontaining 1 to 4 nitrogen atom(s), 1 to 2 oxygen atom(s) and/or 1sulfur atom as a substituent of Ar′ is pyrrole, imidazole, triazole,tetrazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine,azepine, diazepine, furan, pyran, oxepine, oxazepine, thiophene, thiain(thiopyran), thiepine, oxazole, isoxazole, thiazole, isothiazole,oxadiazole, oxazine, oxadiazine, oxazepine, oxadiazepine, thiadiazole,thiaazine, thiadiazine, thiazepine, thiadiazepine, indole, isoindole,benzofuran, isobenzofuran, benzothiophene, isobenzothiophene, indazole,quinoline, isoquinoline, phthalazine, naphthyridine, quinoxaline,quinazoline, cinnoline, benzoxazole, benzothiazole, benzimidazole ring,etc.

In the present invention, 5 to 10 membered mono- or bi-heterocyclic ringpartially or fully saturated one thereof is pyrroline, pyrrolidine,imidazoline, imidazolidine, triazoline, triazolidine, tetrazoline,tetrazolidine, pyrazoline, pyrazolidine, piperidine, piperazine,tetrahydropyridine, tetrahydropyrimidine, tetrahydropyridazine,dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran,dihydrothiophene, tetrahydrothiophene, dihydrothiain (dihydrothiopyran),tetrahydrothiain (tetrahydrothiopyran), oxazoline (dihydrooxazole),oxazolidine (tetrahydrooxazole), dihydroisoxazole, tetrahydroisoxazole,oxadiazoline (dihydrooxadiazole), oxadiazolidine (tetrahydrooxadiazole),thiazoline (dihydrothiazole), thiazolidine (tetrahydrothiazole),dihydroisothiazole, tetrahydroisothiazole, morpholine, thiomorpholine,indoline, isoindoline, dihydrobenzofuran, perhydrobenzofuran,dihydroisobenzofuran, perhydroisobenzofuran, dihydrobenzothiophene,perhydrobenzothiophene, dihydroisobenzothiophene,perhydroisobenzothiophene, dihydroindazole, perhydroindazole,dihydroquinoline, tetrahydroquinoline, perhydroquinoline,dihydroisoquinoline, tetrahydroisoquinoline, perhydroisoquinoline,dihydrophthalazine, tetrahydrophthalazine, perhydrophthalazine,dihydronaphthyridine, tetrahydronaphthyridine, perhydronaphthyridine,dihydroquinoxaline, tetrahydroquinoxaline, perhydroquinoxaline,dihydroquinazoline, tetrahydroquinazoline, perhydroquinazoline,dihydrocinnoline, tetrahydrocinnoline, perhydrocinnoline,dihydrobenzoxazole, perhydrobenzoxazole, dihydrobenzothiazole,perhydrobenzothiazole, dihydrobenzimidazole, perhydrobenzimidazole,benzofurazane, benzothiadiazole, benzotriazole, imidazothiazole,dioxolane, dioxane, dioxadine ring, etc.

In the present invention, Ar′ is preferably 5 to 10 membered basicheterocyclic ring containing 1 to 4 nitrogen atom(s), and thiazole,isothiazole, isoxazole, pyrazine, pyrimidine, pyridazine, pyridine,pyrrol, imidazole, pyrazole, triazole, indole, indoline, purine,quinoline, isoquinoline, phthalazine, naphthyridine, quinoxaline,cinnoline, pyrrolidine, pyrroline, imidazolidine, imidazoline andpyrazoline ring are more preferable. Most preferable are pyridine orthiazole ring.

The starting materials and reagents in the present invention are knownper se or may be prepared by known methods. The compounds of formulae(III), (IV), (V), (VIII) and (X) are known per se or may be prepared byknown methods.

In each reaction in the present specification, obtained products may bepurified by known techniques. For example, purification may be carriedout by distillation at atmospheric or reduced pressure, by highperformance liquid chromatography, by thin layer chromatography or bycolumn chromatography using silica gel or magnesium silicate, by washingor by recrystallization. Purification may be carried out after eachreaction, or after a series of reactions.

Pharmacological Activity of the Compounds of the Present Invention:

The compound of formula (I) of the present invention can bind stronglyto the EP₁ receptor which is a subtype of prostaglandin E₂ receptor andshows an antagonistic activity. As mentioned hereinbefore, it is knownthat the EP₁ receptor relates to induction pain, pyrexia (inductionfever), diuresis or bladder contractive activity. The compound offormula (I), an ester thereof and a non-toxic salt thereof, which canantagonize this receptor, are therefore useful as analgesics, asantipyretic agents or as agents for the prevention and/or treatment ofpollakiuria (neurogenic bladder, nervous bladder, stimulated bladder(irritable bladder), detrusor instability, dysuria accompanyprostatomegaly), acraturesis (urinary incontinence), lower urinary tractdisease syndrome. In addition, the compound of the present inventionscarcely binds to the other subtypes of PGE₂ and is expected to providean agent with no side effect.

It has also been known that an EP₁ antagonist possesses a suppressiveeffect on aberrantcryptfoci and formation of intestinal polyps,accordingly it indicates an effective anti-tumor activity.

The experiment described below shows evidently that the compound of thepresent invention is less affected by protein binding, so it has asatisfactory in vivo activity.

Pharmacological Experimental Test (i) Binding Assay Using ExpressionCell of Prostanoid Receptor Subtype

The preparation of membrane fraction was carried out according to themethod of Sugimoto et al. (J. Biol. Chem., 267, 6463-6466 (1992)), usingexpression CHO cell of prostanoid receptor subtype (mouse EP₁, EP₂,EP_(3α) or EP₄).

The standard assay mixture containing membrane fraction (0.5 mg/ml) and³H-PGE₂ in a final volume of 200 μl was incubated for 1 hour at roomtemperature. The reaction was terminated by addition of ice-cold buffer(3 ml). The mixture was rapidly filtered through a glass filter (GF/B).The radioactivity associated with the filter was measured by liquidscintillation counting.

K_(d) and B_(max) values were determined from Scatchard plots (Ann. N.Y.Acad. Sci., 51, 660 (1949)). Non-specific binding was calculated as thebinding in the presence of an excess (2.5 μM) of unlabeled PGE₂. In theexperiment for competition of specific ³H-PGE₂ binding by the compoundof the present invention, ³H-PGE₂ (2.5 nM) and the compound of thepresent invention were added. The following buffer was used in allreaction.

Buffer: potassium phosphate (pH 6.0, 10 mM), EDTA (1 mM), MgCl₂ (10 mM)and NaCl (0.1 M).

The dissociation constant K_(i) (μM) of each compound was calculated bythe following equation.

Ki=IC ₅₀/(1+([C]/Kd))

wherein [C] is concentration of ³H-PGE₂ used in the reaction

The results are shown in Table 1.

TABLE 1 Compounds Ki (μM) Compounds of the present invention Example 20.0042 Example 2 (6) 0.00032 Example 2 (32) 0.0079 Example 2 (33) 0.0066Example 2 (41) 0.0015 Example 2 (87) 0.0014 Example 2 (94) 0.0039Example 3 (11) 0.0023 Example 3 (30) 0.0008 Example 4 (14) 0.0008Compounds of the related art (WO98/27053) Example 18 (93) 0.0008 Example18 (113) 0.0055 Example 18 (125) 0.0013 Example 18 (121) 0.0010

Comments:

It is confirmed that the binding affinity of the compound of formula (I)of the present invention to an EP₁ subtype receptor is an equivalent tothat of the compound specifically described in above WO98/27053.

(ii) Experimental Measurement of the Activity of Receptor AntagonismUsing Cells Expressing Prostanoid Receptor Subtype EP₁ in the Presenceof BSA (Bovine Serum Albumin)

The cells expressing mouse EP₁ receptor were seeded at 1×10⁴ cells/wellin 96 well plates and cultured for 2 days with 10% FBS (fetal bovineserum)/minimum essential medium Eagle alpha modification (αMEM) in theincubator (37° C., 5% CO₂). The cells in each well were rinsed withphosphate buffer (PBS(−)), and load buffer was added. After incubationfor 1 hour, the load buffer was discarded. After the addition of theassay buffer to each well, the cells were incubated in a dark place atroom temperature for 1 hour. After the addition of a compound of thepresent invention (10 μl) and PGE₂ (10 μl) which were prepared withassay buffer, intracellular calcium concentration was measured withFluorescence drug screening system (FDSS-4000, Hamamatsu Photonics). Apair of fluorescence intensities emitted 500 nm by an excitationwavelength of each 340 nm and 380 nm was measured.

The EP₁ antagonist activity was estimated as percent inhibition of theincrease of intracellular calcium concentration induced by PGE₂ (100nM).

Load buffer: 10% FBS/αMEM containing 5 μM of Fura 2/AM, 20 μM ofindomethacin, 2.5 mM of probenecidAssay buffer: Hank's balanced salt solution (HBSS) containing 1% (w/v)BSA, 2 μM of indomethacin, 2.5 mM of probenecid and 10 mM of HEPES-NaOH

The results are shown in Table 2.

TABLE 2 Compounds IC₅₀ (μM) Compounds of the present invention Example 20.0078 Example 2 (6) 0.0072 Example 2 (32) 0.021 Example 2 (33) 0.0041Example 2 (41) 0.025 Example 2 (87) 0.0073 Example 2 (94) 0.0092 Example3 (11) 0.0049 Example 3 (30) 0.0037 Example 4 (14) 0.0071 Compounds ofthe related art (WO98/27053) Example18 (93) 0.20 Example18 (113) 0.47Example18 (125) 1.34 Example18 (121) 0.26

Comments:

In the experiment coexistent with proteins (measurement of activity ofsignaling in cells), the compound of formula (I) of the presentinvention indicated ten fold as high activity of inhibition of signalingas the compound specifically described in WO98/27053 or more.

It shows that the compound specifically described in WO98/27053 isaffected by protein binding to descend its activity in coexistence withserum protein. On the other hand, it also shows that all of thecompounds of formula (I) of the present invention are less affected bycoexistent protein, and its activity is less lowered.

(iii) Experiment to Assess the Inhibition of Sulprostone-InducedIncrease of Intravesical Pressure of Bladder in Rats.

Female rats (Wistar) were anesthetized by urethane and their bothureters were ligated and cut off at the kidney side. The urinary bladderwas incised its top and catheter was inserted. The other end of catheterwas connected to the pressure transducer and the infusion pump. Repeatedmicturition reflex, which was induced by the continuous infusion ofcitrate buffer (pH 3.5) into the bladder, was recorded. The increase ofmicturition pressure was elicited by the subcutaneous injection ofdiclofenac (5 mg/kg) and sulprostone (300 μg/kg). Since such anincreasing effect was not observed by the treatment of EP₃ agonist, itwas considered that this increase was caused by the activation of EP₁receptor. The inhibitory effects of the compound of the presentinvention on this increase of intravesical pressure were measured for 60minutes after the intraduodenal administration (2 ml/kg).

Table 3 shows the percent inhibition of increase of intravesicalpressure at 40 minutes after the administration (1 mg/kg).

TABLE 3 Inhibition (%) Compounds (40 minutes later) Example 2 68 ± 1 Example 2 (33) 79 ± 11

Comments:

It is confirmed that the compound of formula (I) of the presentinvention indicated a stronger suppression effect than that of thecompound specifically described in WO98/27053 in in vivo experiment, andthat it showed effective activity.

(iv) Experiment to Assess the Antagonistic Activity on the Increase inUrination Volume and Number Induced by Sulprostone to Rats.

Male rats (CD (SD) IGS) were used and micturition number and urinationvolume were measured by means of a Micturition volume measurement system(Neuroscience).

A compound of the present invention was orally administrated (4 ml/kg),and 30 minutes later, sulprostone (200 μg/4 ml/kg) was subcutaneouslyadministered. Number and volume of urination were continuously monitoredfor 3 hours from the administration of sulprostone.

The percent inhibition of each compound was calculated by the followingequation.

${{Inhibition}\mspace{14mu} (\%)} = {\frac{\begin{matrix}{( \begin{matrix}{{number}\mspace{14mu} {of}\mspace{14mu} {micturitio}} \\{\; {{in}\mspace{14mu} {control}\mspace{14mu} {group}}}\end{matrix}\mspace{11mu} ) -} \\( \begin{matrix}\begin{matrix}{{number}\mspace{14mu} {of}\mspace{14mu} {micturition}\mspace{14mu} {in}} \\{\; {{test}\mspace{14mu} {compound}\mspace{14mu} {in}\mspace{14mu} {the}}\mspace{14mu}}\end{matrix} \\{{present}\mspace{14mu} {invention}\mspace{14mu} {group}}\end{matrix}\mspace{11mu} )\end{matrix}}{( {{number}\mspace{14mu} {of}\mspace{14mu} {micturition}\mspace{14mu} {in}\mspace{14mu} {control}\mspace{14mu} {group}} )} \times 100}$

Comments:

It is confirmed that the compound of formula (I) of the presentinvention indicated a stronger suppression effect than that of thecompound specifically described in WO98/27053 in in vivo experiment.

Toxicity:

The toxicity of the compound of the present invention is very low andtherefore, it is confirmed that the compound is safe for medical use.

INDUSTRIAL APPLICABILITY Application to Pharmaceuticals

The compound of formula (I) of the present invention, an ester thereofand a non-toxic salt thereof, which antagonize the EP₁ receptor, aretherefore considered to be useful as analgesics, as antipyretic agentsor as agents for the treatment of pollakiuria (neurogenic bladder,nervous bladder, stimulated bladder (irritable bladder), detrusorinstability, dysuria accompany prostatomegaly), acraturesis (urinaryincontinence), lower urinary tract disease syndrome. In addition, thecompound of the present invention scarcely binds to the other subtypesof PGE₂ and is expected to provide an agent with little side effect.

It has also been known that an EP₁ antagonist possesses a suppressiveeffect on aberrantcryptfoci and formation of intestinal polyps,accordingly it indicates an effective anti-tumor activity.

The compound of formula (I) of the present invention and a non-toxicsalt thereof may be administered in combination with other medicamentsfor the purpose of

1) complement and/or enhancement of the prevention and/or treatmenteffect of the compound,2) improvement of the pharmacokinetics and/or the absorption of thecompound, lowering of dose, and/or3) alleviation of a side effect of the compound.

The compound of formula (I) may be administered in combination withother medicaments as a composition in one drug product comprising thesecomponents, or may be separately administered. In the case of theseparated administration, they may be administered simultaneously orwith lapse of time. While administration with lapse of time, thecompound of formula (I) may be precedently administered, followed byadministration of the other medicaments. Alternatively, the othermedicaments may be precedently administered, followed by administrationof the compound of formula (I). Routes of administration may be eitherthe same or different to each other.

The above combination drug takes effect on whichever disease preventingand/or treatment effect of the compound of formula (I) is complementedand/or enhanced.

For example, the other medicaments which complement and/or enhance theeffect of the compound of formula (I) for the prevention and/ortreatment for pollakiuria (frequent urination) are anticholinergicdrugs, tricyclic anti-depressant agents, α agonists, α₁ antagonists,GABA agonists, antidiuretics, anti-androgenic hormones, corpus luteumhormones, NK₁ antagonists, β₃ agonists, P2X antagonists, potassiumchannel openers, LPA, EP₃ antagonists, capsaicin, resiniferatoxin,5α-reductase inhibitors, etc.

For example, other medicaments which are useful for the complementand/or enhancement of the effect of the compound of formula (I) for theprevention and/or treatment of algia are opioids, gabapentin,pregabalin, α₂ antagonists, NMDA antagonists, TTX-resistant sodiumchannel blockers, VR1 antagonists, nociceptin antagonists, P2Xantagonists, IP antagonists, EP₃ antagonists, N-type calcium channelblockers, iNOS inhibitors, etc.

A weight ratio of the compound of formula (I) and other medicaments isnot limited in particular.

The other medicaments may be administered in combination of arbitrarytwo or more.

Based on the mechanism, the other medicaments which complement and/orenhance the effect of the compound of formula (I) for the preventingand/or treatment for disorders include not only medicaments which havealready found thus far but also ones which will be found in future.

For the purpose above described, the compound of formula (I) of thepresent invention, an ester thereof, a non-toxic salt thereof orcombination of theirs and other medicaments may be normally administeredsystemically or partially, usually by oral or parenteral administration.

The dosages are determined depending on patient's age, body weight,symptom, a desired therapeutic effect, a route of administration and aduration of the treatment, etc. Generally the doses per person peradministration to an adult human are from 1 to 100 mg up to severaltimes per day by oral administration. Alternatively, they are from 1 to100 mg up to several times per day by parenteral administration(preferred into vein). Or they are administrated into vein continuouslyfor from 1 to 24 hours per day.

As mentioned above, the doses to be used depend on various conditions.So the doses to be administrated may be lower than the dose specifiedabove in some cases and sometimes they may be something over.

The compound of formula (I) of the present invention and a non-toxicsalt thereof or a combination of the compound of formula (I) and othermedicaments may be administered in the form of, for example, solidcompositions, liquid compositions or other compositions for oraladministration, or as injections, external medicines or suppositories,etc. for parenteral administration.

Solid compositions for oral administration include tablets, pills,capsules, dispersible powders and granules, etc.

Capsules include hard capsules and soft capsules.

In such solid compositions, one or more of the active compound(s) is orare, admixed with at least one inert diluent e.g. lactose, mannitol,glucose, hydroxypropyl cellulose, microcrystalline cellulose, starch,polyvinylpyrrolidone, magnesium metasilicate aluminate, etc. Suchcompositions may contain additional substances other than inert diluent,for example, lubricating agents e.g. magnesium stearate, disintegratingagents e.g. cellulose calcium glycolate, agents for stabilizing e.g.lactose, assisting agents for dissolving e.g. glutamic acid, asparaginicacid. Tablets or pills may, if desired, be coated with gastric orenteric films such as sugar, gelatin, hydroxypropyl cellulose orhydroxypropylmethylcellulose phthalate, etc., or be coated with two ormore films. And further, the compositions also include capsules ofabsorbable materials such as gelatin.

Liquid compositions for oral administration includepharmaceutically-acceptable emulsions, solutions, syrups and elixirs,etc. In such liquid compositions, one or more of the active compound(s)is or are comprised in inert diluent(s) commonly used in the art (e.g.purified water, ethanol). Besides inert diluents, such compositions mayalso comprise adjuvants such as wetting agents, suspending agents,sweetening agents, flavoring agents, perfuming agents, preservingagents.

Other compositions for oral administration include spray compositionswhich may be prepared by known methods per se and which comprise one ormore of the active compound(s). Spray compositions may compriseadditional substances other than inert diluents: e.g. stabilizing agentssuch as sodium hydrogen sulfate, stabilizing agents to give the titlecompound isotonicity, isotonic buffer such as sodium chloride, sodiumcitrate and citric acid. For preparation of such spray compositions, forexample, the method described in the U.S. Pat. Nos. 2,868,691 or3,095,355 may be used.

Injections for parenteral administration include sterile aqueous ornon-aqueous solutions, suspensions and emulsions. Aqueous solutions orsuspensions include, for example, distilled water for injection andphysiological salt solution. Non-aqueous solutions or suspensionsinclude, for example, propylene glycol, polyethylene glycol, plant oilssuch as olive oil, alcohols such as ethanol, POLYSORBATE80 (registeredtrademark), etc. It may be used by admixing of sterile aqueous ornon-aqueous solutions, suspensions and emulsion. Such compositions maycomprise additional diluents: e.g. preserving agents, wetting agents,emulsifying agents, dispersing agents, stabilizing agent (for example,lactose), assisting agents such as assisting agents for dissolving (forexample, glutamic acid, asparaginic acid). They may be sterilized, forexample, by filtration through a bacteria-retaining filter, byincorporation of sterilizing agents in the compositions or byirradiation. They also be manufactured in the form of sterile solidcompositions (for example, the freeze-dried compositions) and which canbe dissolved in sterile water or some other sterile diluents forinjection immediately before usage.

Other compositions for parenteral administration include liquids forexternal use, and endemic liniments, ointment, suppositories andpessaries which comprise one or more of the active compound(s) and maybe prepared by known methods.

BEST MODE FOR CARRYING OUT THE INVENTION

The following Reference examples and Examples are intend to illustrate,but not to limit the present invention.

The solvents in parentheses at chromatographic separations section showthe developing or eluting solvents and the ratios of the solvents usedare indicated by volume. Without special explanation, NMR data wasdetermined in CDCl₃ solution. And the solvents in parentheses at NMRdata section show solvents used in determination.

Reference Example 14-(2-nitro-4,5-dimethylphenoxymethyl)-3-methylbenzoic acid methyl ester

Under atmosphere of argon, a mixture of 2-nitro-4,5-dimethylphenol (4g), DMF (100 ml), potassium carbonate (6.6 g) and4-mesyloxymethyl-3-methylbenzoic acid methyl ester (6.8 g) were stirredfor 15 minutes at 60° C. After the termination of reaction, the mixturewas cooled and poured into iced water. The mixture was extracted withethyl acetate-hexane. The organic layer was washed, dried, concentratedunder reduced pressure to give the title compound (7.22 g) having thefollowing physical data.

TLC: Rf 0.24 (n-hexane:ethyl acetate=4:1).

Reference Example 24-(2-amino-4,5-dimethylphenoxymethyl)-3-methylbenzoic acid methyl ester

A mixture of 4-(2-nitro-4,5-dimethylphenoxymethyl)-3-methylbenzoic acidmethyl ester prepared in Reference Example 1 (7.21 g), acetic acid (88ml) and water (8.8 ml) was stirred at 50° C. To the reaction solution,iron powder (6.11 g) was gradually added, and the mixture was stirredfor 1 hour at 50° C. After cooling, the mixture was filtered and thefiltrate was concentrated and azeotroped with toluene. To the residue,ethyl acetate-water (100 ml-100 ml) was added and the mixture wasfiltrated over Celite (registered trademark). The organic layer waswashed, dried, concentrated under reduced pressure to give the titlecompound (4.66 g) having the following physical data.

TLC: Rf 0.51 (n-hexane:ethyl acetate=2:1).

Reference Example 33-methyl-4-[2-[N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid methyl ester

A solution of 4-(2-amino-4,5-dimethylphenoxymethyl)-3-methylbenzoic acidmethyl ester prepared in Reference Example 2 (632 mg) in pyridine (4 ml)was cooled to 0° C., then 5-methylfuran-2-sulfonyl chloride (490 mg) wasadded dropwise thereto. After the solution was stirred for 1 hour atroom temperature, the reaction mixture was diluted by ethyl acetate, andpoured into water. The organic layer was washed, dried, concentratedunder reduced pressure. The residue was washed by mixed solvent ofdiisopropylether and hexane to give the title compound (875 mg) havingthe following physical data.

TLC: Rf 0.42 (n-hexane:ethyl acetate=2:1).

Example 13-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid methyl ester

To a solution of3-methyl-4-[2-[N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid methyl ester prepared in Reference Example 3 (870 mg) inN,N-dimethylacetamide (2 ml), cesium carbonate (1.37 g) and isobutyliodide (0.36 ml) were added and the mixture was stirred for 1 hour at100° C. The reaction mixture was allowed to cool and poured into ethylacetate-water (40 ml-40 ml). The organic layer was washed, dried andconcentrated under reduced pressure.

The residue was purified by column chromatography on silica gel(toluene-ethyl acetate) to give the title compound (855 mg) having thefollowing physical data.

TLC: Rf 0.51 (n-hexane:ethyl acetate=2:1);

NMR: δ 7.87 (d, J=8.4 Hz, 1H), 7.86 (s, 1H), 7.38 (d, J=8.4 Hz, 1H),7.04 (s, 1H), 6.70 (m, 2H), 5.93 (m, 1H), 4.91 (brs, 2H), 3.92 (s, 3H),3.48 (m, 2H), 2.34 (s, 3H), 2.23 (s, 3H), 2.18 (s, 3H), 2.09 (s, 3H),0.90 (brs, 6H).

Example 23-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

To a solution of3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid methyl ester prepared in Example 1 (850 mg) in dioxane (10 ml), 2Naqueous sodium hydroxide (2.5 ml) and methanol (4 ml) were added, andthe mixture was stirred for 30 hours at room temperature. To themixture, 2N hydrochloric acid was added, then ethyl acetate-water (30ml-15 ml) was also added. The organic layer was washed, dried andconcentrated under reduced pressure. The residue was dissolved in hotethanol (40 ml) and added by hot water (40 ml), then allowed to cool.Precipitation was filtrated, and dried to give the title compound (755mg) having the following physical data.

TLC: Rf 0.78 (chloroform:methanol:water=8:2:0.2);

NMR: δ 7.94 (d, J=7.8 Hz, 1H), 7.93 (s, 1H), 7.44 (d, J=7.8 Hz, 1H),7.04 (s, 1H), 6.74-6.70 (m, 2H), 5.94 (dd, J=3.3, 0.9 Hz, 1H), 4.94 (br,2H), 3.48 (d, J=6.6 Hz, 2H), 2.37 (s, 3H), 2.24 (s, 3H), 2.19 (s, 3H),2.11 (s, 3H), 1.68 (sep, J=6.6 Hz, 1H), 0.91 (d, J=6.6 Hz, 6H).

Example 2(1) to Example 2(124)

By the same procedures as described in Reference Example 1 to 3,Examples 1 and 2 using corresponding compounds, the title compoundshaving the following physical data were obtained.

Example 2(1)4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamicacid

TLC: Rf 0.51 (n-hexane:ethyl acetate:acetic acid=1:1:0.02);

NMR: δ 7.80 (d, J=16.2 Hz, 1H), 7.59 (d, J=8.0 Hz, 2H), 7.45-7.36 (m,3H), 7.26 (dd, J=8.2, 1.8 Hz, 1H), 7.18 (d, J=1.8 Hz, 1H), 7.00-5.00(br, 1H), 6.75 (d, J=3.4 Hz, 1H), 6.49 (d, J=16.2 Hz, 1H), 5.98 (dq,J=3.4, 0.8 Hz, 1H), 5.05 (brs, 2H), 3.51 (d, J=7.4 Hz, 2H), 2.16 (s,3H), 1.75-1.50 (m, 1H), 0.88 (d, J=6.8 Hz, 6H).

Example 2(2)4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoicacid

TLC: Rf 0.44 (chloroform:methanol=9:1);

NMR: δ 8.16 (d, J=8.4 Hz, 2H), 7.60 (d, J=8.4 Hz, 2H), 7.21-7.26 (m,3H), 6.84 (d, J=3.2 Hz, 1H), 6.05 (m, 1H), 5.21 (m, 2H), 4.49 (m, 1H),2.33 (s, 3H), 1.10 (d, J=6.6 Hz, 6H).

Example 2(3)4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoicacid

TLC: Rf 0.46 (chloroform:methanol=9:1);

NMR: δ 8.15 (d, J=8.6 Hz, 2H), 7.46 (d, J=8.6 Hz, 2H), 7.41 (m, 1H),7.29 (m, 1H), 7.18 (m, 1H), 6.76 (d, J=3.4 Hz, 1H), 5.98 (m, 1H), 5.10(s, 2H), 3.51 (d, J=6.2 Hz, 2H), 2.16 (s, 3H), 1.64 (m, 1H), 0.90 (d,J=6.8 Hz, 6H).

Example 2(4)4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid

TLC: Rf 0.30 (chloroform:methanol=9:1);

NMR: δ 8.12 and 7.46 (each d, J=8.1 Hz, each 2H), 7.20 (s, 1H),6.81-6.75 (m, 2H), 6.01-5.98 (m, 1H), 5.12-4.98 (m, 2H), 3.45 (d, J=7.5Hz, 2H), 2.34 and 2.19 (each s, each 3H), 1.75-1.59 (m, 1H), 0.91 (d,J=6.9 Hz, 6H).

Example 2(5)4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.38 (chloroform:methanol=10:1);

NMR: δ 8.12-8.09 (m, 2H), 7.56 (d, J=8.4 Hz, 2H), 6.81 (s, 1H), 6.79 (d,J=3.3 Hz, 1H), 6.75 (s, 1H), 6.02 (dd, J=3.3, 1.2 Hz, 1H), 5.10 (s, 2H),4.48 (m, 1H), 2.30 (s, 3H), 2.23 (s, 3H), 2.17 (s, 3H), 1.11 (d, J=6.6Hz, 6H).

Example 2(6)4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.38 (chloroform:methanol=10:1);

NMR: δ 8.12-8.08 (m, 2H), 7.42 (d, J=8.4 Hz, 2H), 7.03 (s, 1H), 6.71 (d,J=3.3 Hz, 1H), 6.68 (s, 1H), 5.92 (dd, J=3.3, 0.9 Hz, 1H), 5.00 (brs,2H), 3.52-3.46 (m, 2H), 2.22 (s, 3H), 2.18 (s, 3H), 2.13 (s, 3H), 1.68(m, 1H), 0.91 (d, J=6.6 Hz, 6H).

Example 2(7)3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid

TLC: Rf 0.42 (chloroform:methanol 9:1);

NMR: δ 8.00-7.89 (m, 2H), 7.41 (d, J=8.4 Hz, 1H), 7.16 (s, 1H), 6.95 (s,1H), 6.74 (d, J=3.3 Hz, 1H), 5.96 (m, 1H), 4.94 (s, 2H), 3.47 (d, J=6.3Hz, 2H), 2.37 (s, 3H), 2.30 (s, 3H), 2.11 (s, 3H), 1.64 (m, 1H), 0.90(d, J=6.6 Hz, 6H).

Example 2(8)3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid

TLC: Rf 0.58 (chloroform:methanol=9:1);

NMR: δ 7.96 (d, J=7.5 Hz, 1H), 7.94 (s, 1H), 7.47 (d, J=7.5 Hz, 1H),7.20 (s, 1H), 6.81 (s, 1H), 6.77 (d, J=3.3 Hz, 1H), 6.03-5.97 (m, 1H),4.99 (brs, 2H), 3.44 (d, J=7.5 Hz, 2H), 2.39 (s, 3H), 2.36 (s, 3H), 2.17(s, 3H), 1.75-1.60 (m, 1H), 0.89 (d, J=6.6 Hz, 6H).

Example 2(9)3-chloro-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid

TLC: Rf 0.38 (chloroform:methanol=9:1);

NMR: δ 8.13 (d, J=1.5 Hz, 1H), 8.02 (dd, J=8.4, 1.5 Hz, 1H), 7.58 (d,J=8.4 Hz, 1H), 7.15 (s, 1H), 6.94 (s, 1H), 6.76 (d, J=3.3 Hz, 1H), 5.98(m, 1H), 5.25-4.90 (br, 2H), 3.48 (d, J=6.6 Hz, 2H), 2.31 (s, 3H), 2.16(s, 3H), 1.64 (m, 1H), 0.92 (d, J=6.6 Hz, 6H).

Example 2(10)3-chloro-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid

TLC: Rf 0.38 (chloroform:methanol=9:1);

NMR: δ 8.12 (d, J=1.5 Hz, 1H), 8.07 (dd, J=8.4, 1.5 Hz, 1H), 7.88 (d,J=8.4 Hz, 1H), 6.99 (s, 1H), 6.95 (s, 1H), 6.85 (d, J=3.3 Hz, 1H), 6.06(m, 1H), 5.20 (d, J=14.4 Hz, 1H), 5.15 (d, J=14.4 Hz, 1H), 4.48 (m, 1H),2.33 (s, 3H), 2.30 (s, 3H), 1.11 (d, J=6.3 Hz, 3H), 1.09 (d, J=6.3 Hz,3).

Example 2(11)3-methoxy-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid

TLC: Rf 0.49 (chloroform:methanol=9:1);

NMR: δ 7.78 (dd, J=8.1, 1.5 Hz, 1H), 7.76 (d, J=1.5 Hz, 1H), 7.59 (d,J=1.5 Hz, 1H), 7.01 (s, 1H), 6.96 (s, 1H), 6.83 (d, J=3.3 Hz, 1H),6.05-6.00 (m, 1H), 5.11 (d, J=14.1 Hz, 1H), 5.07 (d, J=14.1 Hz, 1H),4.55-4.40 (m, 1H), 3.94 (s, 3H), 2.30 (s, 3H), 2.29 (s, 3H), 1.12 (d,J=6.9 Hz, 6H).

Example 2(12)3-methoxy-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.44 (chloroform:methanol=9:1);

NMR: δ 7.77 (dd, J=8.1, 1.2 Hz, 1H), 7.74 (d, J=8.1 Hz, 1H), 7.58 (d,J=1.2 Hz, 1H), 6.84 (s, 1H), 6.81 (d, J=3.3 Hz, 1H), 6.78 (s, 1H),6.05-6.00 (m, 1H), 5.09 (s, 2H), 4.60-4.40 (m, 1H), 3.94 (s, 3H), 2.29(s, 3H), 2.24 (s, 3H), 2.17 (s, 3H), 1.12 (d, J=6.9 Hz, 6H).

Example 2(13)3-methoxy-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.45 (chloroform:methanol=9:1);

NMR: δ 7.73 (dd, J=8.1, 1.2 Hz, 1H), 7.58 (d, J=1.2 Hz, 1H), 7.40 (d,J=8.1 Hz, 1H), 7.07 (s, 1H), 6.75-6.70 (m, 2H), 5.95-5.90 (m, 1H),5.15-4.85 (m, 2H), 3.94 (s, 3H), 3.51 (br, 2H), 2.23 (s, 3H), 2.19 (s,3H), 2.11 (s, 3H), 1.80-1.60 (m, 1H), 0.94 (br, 6H).

Example 2(14)3-methoxy-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid

TLC: Rf 0.46 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 13.02 (s, 1H), 7.58-7.50 (m, 3H), 7.24 (s, 1H), 6.98 (s,1H), 6.94 (d, J=3.3 Hz, 1H), 6.25 (m, 1H), 5.10 (d, J=13.5 Hz, 1H), 5.04(d, J=13.5 Hz, 1H), 4.24 (m, 1H), 3.87 (s, 3H), 2.34 (s, 3H), 2.27 (s,3H), 0.99 (d, J=6.6 Hz, 3H), 0.98 (d, J=6.6 Hz, 3H).

Example 2(15)3-chloro-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.40 (chloroform:methanol=9:1);

NMR: δ 8.12 (d, J=1.8 Hz, 1H), 8.02 (dd, J=8.1, 1.8 Hz, 1H), 7.61 (d,J=8.1 Hz, 1H), 7.03 (s, 1H), 6.75 (d, J=3.3 Hz, 1H), 6.70 (s, 1H), 5.96(m, 1H), 5.25-4.85 (br, 2H), 3.50 (d, J=6.6 Hz, 2H), 2.24 (s, 3H), 2.19(s, 3H), 2.16 (s, 3H), 1.79 (m, 1H), 0.93 (d, J=6.6 Hz, 6H).

Example 2(16)3-chloro-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.39 (chloroform:methanol=9:1);

NMR: δ 8.11 (d, J=1.8 Hz, 1H), 8.06 (dd, J=8.1, 1.8 Hz, 1H), 7.90 (d,J=8.1 Hz, 1H), 6.86-6.80 (m, 2H), 6.75 (s, 1H), 6.05 (m, 1H), 5.17 (s,2H), 4.51 (m, 1H), 2.32 (s, 3H), 2.25 (s, 3H), 2.18 (s, 3H), 1.12 (d,J=6.6 Hz, 3H), 1.11 (d, J=6.6 Hz, 3H).

Example 2(17)3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]cinnamicacid

TLC: Rf 0.37 (chloroform:methanol=9:1);

NMR(CD₃OD): δ 7.63 (d, J=16.2 Hz, 1H), 7.45 (s) and 7.44 (d, J=8.1 Hz)total 2H, 7.34 (d, J=8.1 Hz, 1H), 7.17 (s, 1H), 7.10 (s, 1H), 6.72 (d,J=3.3 Hz, 1H), 6.50 (d, J=16.2 Hz, 1H), 6.08 (dd, J=3.3, 1.2 Hz, 1H),4.98 (brs, 2H), 3.44 (d, J=6.9 Hz, 2H), 2.37 (s, 3H), 2.35 (s, 3H), 2.10(s, 3H), 1.60 (m, 1H), 0.87 (d, J=6.6 Hz, 6H).

Example 2(18)4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamicacid

TLC: Rf 0.31 (chloroform:methanol=9:1);

NMR: δ 7.73 (d, J=15.9 Hz, 1H), 7.57 and 7.49 (each d, J=8.1 Hz, each2H), 6.98 and 6.92 (each s, each 1H), 6.81 (d, J=3.3 Hz, 1H), 6.46 (d,J=15.9 Hz, 1H), 6.03 (d, J=3.3 Hz, 1H), 5.05 (s, 2H), 4.50-4.38 (m, 1H),2.30 and 2.28 (each s, each 3H), 1.10 and 1.09 (each d, J=6.6 Hz, each3H).

Example 2(19)4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamicacid

TLC: Rf 0.31 (chloroform:methanol=9:1);

NMR: δ 7.77 (d, J=15.9 Hz, 1H), 7.56 and 7.35 (each d, J=7.8 Hz, each2H), 7.14 and 6.92 (each s, each 1H), 6.72 (d, J=3.6 Hz, 1H), 6.47 (d,J=15.9 Hz, 1H), 5.95 (d, J=3.6 Hz, 1H), 5.00-4.88 (m, 2H), 3.52-3.42 (m,2H), 2.29 and 2.13 (each s, each 3H), 1.72-1.60 (m, 1H), 0.90 (d, J=6.3Hz, 6H).

Example 2(20)4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid

TLC: Rf 0.39 (chloroform:methanol=9:1);

NMR: δ 7.78 (d, J=15.9 Hz, 1H), 7.57 (d, J=8.4 Hz, 2H), 7.50 (d, J=8.4Hz, 2H), 6.80 (s, 1H), 6.79 (d, J=3.3 Hz, 1H), 6.76 (s, 1H), 6.46 (d,J=15.9 Hz, 1H), 6.01 (m, 1H), 5.06 (s, 2H), 4.47 (sept, J=6.6 Hz, 1H),2.30 (s, 3H), 2.23 (s, 3H), 2.16 (s, 3H), 1.11 and 1.10 (each d, J=6.6Hz, each 3H).

Example 2(21)3-methyl-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamicacid

TLC: Rf 0.42 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 12.36 (br s, 1H), 7.61-7.52 (m, 5H), 7.38 (d, J=8.0 Hz,1H), 7.24 (d, J=8.0 Hz, 1H), 6.96 (d, J=3.5 Hz, 1H), 6.54 (d, J=16.0 Hz,1H), 6.28 (d, J=3.5 Hz, 1H), 5.24 (d, J=13.0 Hz, 1H), 5.18 (d, J=13.0Hz, 1H), 4.26 (septet, J=6.5 Hz, 1H), 2.35 (s, 3H), 2.30 (s, 3H), 0.97(d, J=6.5 Hz, 6H).

Example 2(22)3-methyl-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.28 (n-hexane:ethyl acetate=1:1);

NMR: δ 7.97 (d, J=7.8 Hz, 1H), 7.93 (s, 1H), 7.65 (d, J=7.8 Hz, 1H),6.82 (s, 1H), 6.79 (d, J=3.3 Hz, 1H), 6.77 (s, 1H), 6.01 (dd, J=3.3, 1.2Hz, 1H), 5.08 (d, J=13.2 Hz, 1H), 5.02 (d, J=13.2 Hz, 1H), 4.47 (quint,J=6.6 Hz, 1H), 2.40 (s, 3H), 2.29 (s, 3H), 2.25 (s, 3H), 2.17 (s, 3H),1.11 (d, J=6.6 Hz, 6H).

Example 2(23)3-methyl-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid

TLC: Rf 0.30 (n-hexane:ethyl acetate=1:2);

MS (FAB, Pos.): 498 (M+H)⁺.

Example 2(24)3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid

TLC: Rf 0.26 (n-hexane:ethyl acetate=1:2);

MS (FAB, Pos.): 512 (M+H)⁺.

Example 2(25)4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid

TLC: Rf 0.47 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.69 (d, J=8.1 Hz, 2H), 7.58 (d, J=16.2 Hz, 1H), 7.34(d, J=8.1 Hz, 2H), 6.93 (s, 1H), 6.90 (s, 1H), 6.79 (d, J=3.3 Hz, 1H),6.54 (d, J=16.2 Hz, 1H), 6.13 (m, 1H), 5.10-4.80 (m, 2H), 3.40-3.20 (m,2H, covered with H₂O in DMSO-d₆), 2.18 (s, 3H), 2.11 (s, 3H), 2.10 (s,3H), 1.58-1.42 (m, 1H), 0.82 (d, J=6.6 Hz, 6H).

Example 2(26)3-methoxy-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamicacid

TLC: Rf 0.30 (chloroform:methanol=9:1);

NMR: δ 7.76 (d, J=15.9 Hz, 1H), 7.30 (d, J=8.1 Hz, 1H), 7.26 (s, 1H),7.20 (d, J=8.1 Hz, 1H), 7.04 (s, 1H), 6.96 (s, 1H), 6.72 (d, J=3.3 Hz,1H), 6.46 (d, J=15.9 Hz, 1H), 6.00-5.90 (m, 1H), 4.95 (brs, 2H), 3.91(s, 3H), 3.48 (brs, 2H), 2.29 (s, 3H), 2.13 (s, 3H), 1.75-1.60 (m, 1H),0.91 (brd, J=6.6 Hz, 6H).

Example 2(27)4-[6-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.45 (chloroform:methanol=9:1);

NMR: δ 8.11 (d, J=8.1 Hz, 2H), 7.43 (d, J=8.1 Hz, 2H), 7.12 (s, 1H),6.77 (s, 1H), 6.73 (d, J=3.3 Hz, 1H), 5.94 (m, 1H), 5.15-4.85 (br, 2H),3.60-3.40 (br, 2H), 2.86 (t, J=7.2 Hz, 4H), 2.14 (s, 3H), 2.13-2.00 (m,2H), 1.68 (m, 1H), 1.02-0.82 (br, 6H).

Example 2(28)4-[6-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.45 (chloroform:methanol=9:1);

NMR: δ 8.12 (d, J=8.4 Hz, 2H), 7.57 (d, J=8.4 Hz, 2H), 6.90 (s, 1H),6.83 (s, 1H), 6.81 (d, J=3.3 Hz, 1H), 6.02 (m, 1H), 5.17-5.05 (m, 2H),4.49 (m, 1H), 2.93-2.79 (m, 4H), 2.31 (s, 3H), 2.15-2.00 (m, 2H), 1.12(d, J=6.6 Hz, 3H), 1.11 (d, J=6.6 Hz, 3H).

Example 2(29)4-[7-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-1,2,3,4-tetrahydronaphthalen-6-yloxymethyl]benzoicacid

TLC: Rf 0.45 (chloroform:methanol=9:1);

NMR: δ 8.10 (d, J=8.1 Hz, 2H), 7.42 (d, J=8.1 Hz, 2H), 6.95 (s, 1H),6.73 (d, J=3.3 Hz, 1H), 6.57 (s, 1H), 5.93 (m, 1H), 5.15-4.82 (br, 2H),3.48 (d, J=7.2 Hz, 2H), 2.77-2.60 (m, 4H), 2.13 (s, 3H), 1.82-1.60 (m,5H), 0.92 (d, J=6.6 Hz, 6H).

Example 2(30)4-[7-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-1,2,3,4-tetrahydronaphthalen-6-yloxymethyl]benzoicacid

TLC: Rf 0.45 (chloroform:methanol=9:1);

NMR: δ 8.12 (d, J=8.4 Hz, 2H), 7.56 (d, J=8.4 Hz, 2H), 6.80 (d, J=3.3Hz, 1H), 6.74 (s, 1H), 6.64 (s, 1H), 6.02 (m, 1H), 5.16-5.04 (m, 2H),4.48 (m, 1H), 2.77-2.58 (m, 4H), 2.30 (s, 3H), 1.82-1.69 (m, 4H), 1.12(d, J=6.6 Hz, 3H), 1.11 (d, J=6.6 Hz, 3H).

Example 2(31)3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamicacid

TLC: Rf 0.30 (chloroform:methanol=9:1);

NMR(CD₃OD): δ 7.65 (d, J=15.9 Hz, 1H), 7.46 (s) and 7.44 (d, J=7.8 Hz)total 2H, 7.34 (d, J=7.8 Hz, 1H), 7.18 (s, 1H), 7.14 (s, 1H), 6.71 (d,J=3.3 Hz, 1H), 6.50 (d, J=15.9 Hz, 1H), 6.07 (dd, J=3.3, 0.9 Hz, 1H),4.95 (m, 2H), 3.44 (d, J=7.5 Hz, 2H), 2.35 (s, 3H), 2.28 (s, 3H), 2.09(s, 3H), 1.61 (m, 1H), 0.87 (d, J=6.6 Hz, 6H).

Example 2(32)4-[6-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.42 (chloroform methanol=9:1);

NMR: δ 7.79 (d, J=15.9 Hz, 1H), 7.55 (d, J=8.1 Hz, 2H), 7.37 (d, J=8.1Hz, 2H), 7.11 (s, 1H), 6.78 (s, 1H), 6.71 (d, J=3.3 Hz, 1H), 6.47 (d,J=15.9 Hz, 1H), 5.93 (m, 1H), 5.10-4.80 (br, 2M), 3.60-3.40 (br, 2H),2.86 (t, J=7.5 Hz, 4H), 2.14 (s, 3H), 2.08 (m, 2H), 1.68 (m, 1H),1.00-0.82 (br, 6H).

Example 2(33)3-methyl-4-[6-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.33 (chloroform:methanol=10:1);

NMR(CDCl₃+1 drop of CD₃OD): δ 7.89 (d, J=8.4 Hz, 1H), 7.88 (s, 1H), 7.39(d, J=8.4 Hz, 1H), 7.12 (s, 1H), 6.79 (s, 1H), 6.71 (d, J=3.3 Hz, 1H),5.94 (m, 1H), 5.06-4.74 (m, 2H), 3.60-3.37 (m, 2H), 2.92-2.82 (m, 4H),2.34 (s, 3H), 2.17-2.03 (m, 2H), 2.10 (s, 3H), 1.69 (m, 1H), 1.01-0.80(m, 6H).

Example 2(34)3-methyl-4-[6-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.30 (chloroform:methanol=10:1);

NMR: δ 7.78 (d, J=15.9 Hz, 1H), 7.42-7.36 (m, 3H), 7.10 (s, 1H), 6.80(s, 1H), 6.72 (d, J=3.3 Hz, 1H), 6.46 (d, J=15.9 Hz, 1H), 5.94 (m, 1H),5.04-4.77 (m, 2H), 3.59-3.37 (m, 2H), 2.91-2.82 (m, 4H), 2.34 (s, 3H),2.14-2.05 (m, 2H), 2.12 (s, 3H), 1.68 (m, 1H), 1.00-0.82 (m, 6H).

Example 2(35)4-[2-[N-(2-methyl-2-propenyl)-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.42 (chloroform:methanol=10:1);

NMR: δ 8.11 (d, J=8.1 Hz, 2H), 7.42 (d, J=8.1 Hz, 2H), 7.02 (s, 1H),6.74 (d, J=3.3 Hz, 1H), 6.67 (s, 1H), 6.00-5.95 (m, 1H), 5.00 (brs, 2H),4.77 (s, 2H), 4.26 (brs, 2H), 2.21 (s, 3H), 2.17 (s, 3H), 2.13 (s, 3H),1.78 (s, 3H).

Example 2(36)4-[2-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoicacid

TLC: Rf 0.58 (ethyl acetate);

NMR(CD₃OD): δ 8.03 (d, J=8.7 Hz, 2H), 7.92 (d, J=3.3 Hz, 1H), 7.82 (d,J=3.3 Hz, 1H), 7.54 (d, J=8.4 Hz, 2H), 7.43 (brs, 1H), 7.37 (d, J=8.1Hz, 1H), 7.30 (brd, J=8.1 Hz, 1H), 5.23 (ABd, J=12.6 Hz) and 5.14 (ABd,J=12.6 Hz) total 2H, 4.64 (sept, J=6.9 Hz, 1H), 1.15 (d, J=6.9 Hz) and1.14 (d, J=6.9 Hz) total 6H.

Example 2(37)4-[2-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoicacid

TLC: Rf 0.60 (ethyl acetate);

NMR(CD₃OD): δ 8.02 (d, J=8.7 Hz, 2H), 7.74 (m, 2H), 7.52 (d, J=7.2 Hz,1H), 7.38 (d, J=8.7 Hz) and 7.37 (s) total 3H, 7.32 (brd, J=7.2 Hz, 1H),5.02 (br, 2H), 3.60 (brd, J=7.5 Hz, 2H), 1.70-1.58 (m, 1H), 0.92 (d,J=6.9 Hz, 6H).

Example 2(38)4-[2-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamicacid

TLC: Rf 0.42 (chloroform:methanol=9:1);

NMR(CD₃OD): δ 7.91 (d, J=3 Hz, 1H), 7.81 (d, J=3 Hz, 1H), 7.69 (d,J=15.9 Hz, 1H), 7.63 (d, J=8.4 Hz, 2H), 7.48 (d, J=8.4 Hz, 2H), 7.42 (s,1H), 7.36 (d, J=8.1 Hz, 1H), 7.29 (brd, J=8.1 Hz, 1H), 6.52 (d, J=15.9Hz, 1H), 5.18 (ABd, J=12.3 Hz) and 5.09 (ABd, J=12.3 Hz) total 2H, 4.63(sept, J=6.6 Hz, 1H), 1.15 (d, J=6.6 Hz) and 1.13 (d, J=6.6 Hz) total6H.

Example 2(39)4-[2-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamicacid

TLC: Rf 0.42 (chloroform:methanol=9:1);

NMR(CD₃OD): δ 7.76-7.70 (m, 2H), 7.64 (s) and 7.63 (d, J=15.9 Hz) total3H, 7.52 (d, J=8.1 Hz, 1H), 7.38-7.28 (m, 4H), 6.53 (d, J=15.9 Hz, 1H),5.04-4.90 (m, 2H), 3.60 (brd, J=6.9 Hz, 2H), 1.72-1.56 (m, 1H), 0.92 (d,J=6.6 Hz, 6H).

Example 2(40)4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoicacid

TLC: Rf 0.42 (chloroform:methanol=9:1);

NMR(CD₃OD): δ 8.03 (d, J=8.4 Hz, 2H), 7.53 (d, J=8.1 Hz, 1H), 7.42-7.30(m) and 7.27 (s) total 5H, 5.18-4.90 (m, 2H), 3.63-3.58 (m, 2H), 2.23(d, J=0.9 Hz, 3H), 1.66 (m, 1H), 0.93 (d, J=6.6 Hz, 6H).

Example 2(41)4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamicacid

TLC: Rf 0.32 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.70 (d, J=8.1 Hz, 2H), 7.60 (d, J=15.9 Hz, 1H),7.56-7.46 (m, 3H), 7.38 (d, J=8.7 Hz, 1H), 7.29 (d, J=8.1 Hz, 2H), 6.56(d, J=15.9 Hz, 1H), 5.20-4.85 (m, 2H), 3.49 (d, J=6.9 Hz, 2H), 2.21 (s,3H), 1.53 (m, 1H), 0.84 (d, J=6.6 Hz, 6H).

Example 2(42)4-[2-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid

TLC: Rf 0.39 (chloroform:methanol=9:1);

NMR: δ 8.13 (d, J=8.1 Hz, 2H), 7.91 (d, J=3.0 Hz, 1H), 7.52 (d, J=8.1Hz, 2H), 7.50 (d, J=3.0 Hz, 1H), 7.10 (s, 1H), 6.85 (s, 1H), 5.09 (s,2H), 4.67 (m, 1H), 2.36 (s, 3H), 1.16 (d, J=6.6 Hz, 3H), 1.15 (d, J=6.6Hz, 3H).

Example 2(43)4-[2-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid

TLC: Rf 0.39 (chloroform:methanol=10:1);

NMR: δ 8.13 (d, J=8.1 Hz, 2H), 7.52 (d, J=8.1 Hz, 2H), 7.09 (s, 1H),7.04 (m, 1H), 6.85 (s, 1H), 5.10 (s, 2H), 4.68 (m, 1H), 2.49 (d, J=0.6Hz, 3H), 2.36 (s, 3H), 1.15 (d, J=6.6 Hz, 3H), 1.14 (d, J=6.6 Hz, 3H).

Example 2(44)4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid

TLC: Rf 0.40 (chloroform:methanol=10:1);

NMR: δ 8.12 (d, J=7.5 Hz, 2H), 7.37 (d, J=7.5 Hz, 2H), 7.27 (d, J=1.2Hz, 1H), 6.96 (m, 1H), 6.78 (s, 1H), 5.10-4.78 (m, 2H), 3.57 (brs, 2H),2.35 (s, 3H), 2.34 (s, 3H), 1.70 (m, 1H), 0.94 (d, J=6.6 Hz, 6H).

Example 2(45)3-chloro-4-[2-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid

TLC: Rf 0.69 (chloroform:methanol:water=8:2:0.2);

NMR: δ 8.12 (d, J=1.5 Hz, 1H), 8.06 (dd, J=8.1, 1.5 Hz, 1H), 7.83 (d,J=8.1 Hz, 1H), 7.11-7.10 (m, 2H), 6.86 (s, 1H), 5.23 (d, J=14.4 Hz, 1H),5.15 (d, J=14.4 Hz, 1H), 4.71 (quint, J=6.6 Hz, 1H), 2.52 (d, J=1.2 Hz,3H), 2.38 (s, 3H), 1.56 (d, J=6.6 Hz, 3H), 1.34 (d, J=6.6 Hz, 3H).

Example 2(46)3-methyl-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoicacid

TLC: Rf 0.44 (chloroform:methanol=9:1);

NMR: δ 7.96 (d, J=8.4 Hz, 1H), 7.95 (s, 1H), 7.48 (d, J=8.1 Hz, 1H),7.35 (d, J=8.4 Hz, 1H), 7.32-7.24 (m, 1H), 7.20 (s, 1H), 6.98 (s, 1H),5.06-4.85 (m, 2H), 3.70-3.50 (m, 2H), 2.39 (s, 3H), 2.34 (s, 3H),1.75-1.59 (m, 1H), 0.91 (d, J=6.6 Hz, 6H).

Example 2(47)3-methyl-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid

TLC: Rf 0.44 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.79 (s, 1H), 7.76 (d, J=8.1 Hz, 1H), 7.56 (s, 1H), 7.29(s, 1H), 7.27 (d, J=8.1 Hz, 1H), 7.23 (s, 1H), 5.20-4.65 (m, 2H),3.55-3.35 (m, 2H), 2.36 (s, 3H), 2.31 (s, 3H), 2.21 (s, 3H), 1.65-1.47(m, 1H), 0.84 (d, J=6.6 Hz, 6H).

Example 2(48)3-methoxy-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid

TLC: Rf 0.48 (chloroform:methanol=9:1);

NMR: δ 7.74 (dd, J=7.8, 1.2 Hz, 1H), 7.59 (d, J=1.2 Hz, 1H), 7.31 (d,J=7.8 Hz, 1H), 7.30 (s, 1H), 6.94 (s, 1H), 6.81 (s, 1H), 5.10-4.70 (m,2H), 3.94 (s, 3H), 3.59 (br, 2H), 2.35 (s, 3H), 2.34 (s, 3H), 1.80-1.60(m, 1H), 1.12 (d, J=6.9 Hz, 6H).

Example 2(49)3-methoxy-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoicacid

TLC: Rf 0.40 (chloroform:methanol=9:1);

NMR: δ 7.73 (dd, J=8.1, 1.5 Hz, 1H), 7.60 (d, J=1.5 Hz, 1H), 7.50 (d,J=8.1 Hz, 1H), 7.34-7.19 (m, 3H), 6.95 (m, 1H), 5.12-4.80 (m, 2H), 3.95(s, 3H), 3.77-3.48 (m, 2H), 2.34 (s, 3H), 1.77-1.60 (m, 1H), 0.94 (d,J=6.6 Hz, 6H).

Example 2(50)4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid

TLC: Rf 0.38 (chloroform:methanol=9:1);

NMR: δ 8.11 and 7.33 (each d, J=8.4 Hz, each 2H), 7.22 (s, 1H), 6.92 and6.91 (each s, each 1H), 5.10-4.70 (m, 2H), 3.74-3.42 (m, 2H), 2.31 and2.30 (each s, each 3H), 1.78-1.62 (m, 1H), 1.05-0.83 (m, 6H).

Example 2(51)3-chloro-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid

TLC: Rf 0.28 (chloroform:methanol=9:1);

NMR: δ 8.11 (s, 1H), 8.02 and 7.45 (each d, J=8.1 Hz, each 1H), 7.21 (s,1H), 6.97 (s, 1H), 6.94 (s, 1H), 5.12-4.74 (m, 2H), 3.75-3.45 (m, 2H),2.32 and 2.31 (each s, each 3H), 1.80-1.62 (m, 1H), 1.05-0.82 (m, 6H).

Example 2(52)3-methoxy-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid

TLC: Rf 0.35 (chloroform:methanol=9:1);

NMR: δ 7.73 (d, J=7.8 Hz, 1H), 7.59 (s, 1H), 7.30-7.20 (m, 2H), 6.95 (s,1H), 6.91 (s, 1H), 5.09-4.62 (m, 2H), 3.94 (s, 3H), 3.78-3.45 (m, 2H),2.31 (s, 6H), 1.79-1.63 (m, 1H), 1.08-0.85 (m, 6H).

Example 2(53)3-methyl-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.76 (chloroform:methanol:water=8:2:0.2);

NMR: δ 7.93 (d, J=8.1 Hz, 1H), 7.92 (s, 1H), 7.30 (d, J=8.1 Hz, 1H),7.08 (s, 1H), 6.90 (d, J=0.9 Hz, 1H), 6.71 (s, 1H), 4.91 (br, 1H), 4.79(br, 1H), 3.65 (br, 1H), 3.56 (br, 1H), 2.35 (s, 3H), 2.30 (d, J=0.9 Hz,3H), 2.24 (s, 3H), 2.19 (s, 3H), 1.71 (sep, J=6.9 Hz, 1H), 1.03-0.92(br, 6H).

Example 2(54)3-methyl-4-[2-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.78 (chloroform:methanol:water=8:2:0.2);

NMR: δ 7.95 (d, J=8.1 Hz, 1H), 7.93 (s, 1H), 7.54 (d, J=8.1 Hz, 1H),6.98 (d, J=0.9 Hz, 1H), 6.86 (s, 1H), 6.78 (s, 1H), 5.03 (d, J=13.2 Hz,1H), 4.98 (d, J=13.2 Hz, 1H), 4.69 (quint, J=6.6 Hz, 1H), 2.46 (d, J=0.9Hz, 3H), 2.39 (s, 3H), 2.25 (s, 3H), 2.16 (s, 3H), 1.17 (d, J=6.6 Hz,3H), 1.13 (d, J=6.6 Hz, 3H).

Example 2(55)3-methoxy-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.39 (chloroform:methanol=9:1);

NMR: δ 7.72 (dd, J=8.1, 1.2 Hz, 1H), 7.57 (d, J=1.2 Hz, 1H), 7.26 (d,J=8.1 Hz, 1H), 7.11 (s, 1H), 6.87 (s, 1H), 6.71 (s, 1H), 4.95 (br, 1H),4.75 (br, 1H), 3.93 (s, 3H), 3.69 (br, 1H), 3.56 (br, 1H), 2.29 (s, 3H),2.23 (s, 3H), 2.19 (s, 3H), 1.80-1.65 (m, 1H), 0.97 (br, 6H).

Example 2(56)3-chloro-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.36 (chloroform:methanol=9:1);

NMR: δ 8.11 (d, J=1.8 Hz, 1H), 8.01 (dd, J=8.1, 1.8 Hz, 1H), 7.49 (d,J=8.1 Hz, 1H), 7.08 (s, 1H), 6.95 (d, J=0.6 Hz, 1H), 6.69 (s, 1H),5.20-4.70 (br, 2H), 3.80-3.45 (br, 2H), 2.32 (d, J=0.6 Hz, 3H), 2.24 (s,3H), 2.19 (s, 3H), 1.75 (m, 1H), 1.07-0.85 (br, 6H).

Example 2(57)3-chloro-4-[2-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.36 (chloroform:methanol=9:1);

NMR(CDCl₃+CD₃OD): δ 8.06 (d, J=1.8 Hz, 1H), 7.98 (dd, J=8.1, 1.8 Hz,1H), 7.70 (d, J=8.1 Hz, 1H), 7.05 (d, J=0.6 Hz, 1H), 6.86 (s, 1H), 6.76(s, 1H), 5.14 (d, J=14.1 Hz, 1H), 5.08 (d, J=14.1 Hz, 1H), 4.70 (m, 1H),2.47 (d, J=0.6 Hz, 3H), 2.25 (s, 3H), 2.17 (s, 3H), 1.17 (d, J=6.6 Hz,3H), 1.15 (d, J=6.6 Hz, 3H).

Example 2(58)4-[2-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.45 (chloroform:methanol=10:1);

NMR: δ 8.11-8.08 (m, 2H), 7.49 (d, J=8.4 Hz, 2H), 6.97 (d, J=0.9 Hz,1H), 6.86 (s, 1H), 6.75 (s, 1H), 5.06 (d, J=12.9 Hz, 1H), 5.04 (d,J=12.9 Hz, 1H), 4.71 (m, 1H), 2.46 (d, J=0.9 Hz, 3H), 2.23 (s, 3H), 2.16(s, 3H), 1.18 (d, J=6.6 Hz, 3H), 1.15 (d, J=6.6 Hz, 3H).

Example 2(59)4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.43 (chloroform:methanol=10:1);

NMR: δ 8.09 (d, J=8.1 Hz, 2H), 7.33 (d, J=8.1 Hz, 2H), 7.08 (s, 1H),6.89 (d, J=0.9 Hz, 1H), 6.68 (s, 1H), 5.08-4.68 (m, 2H), 3.75-3.45 (m,2H), 2.30 (s, 3H), 2.23 (s, 3H), 2.18 (s, 3H), 1.71 (m, 1H), 1.04-0.83(m, 6H).

Example 2(60)4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]cinnamicacid

TLC: Rf 0.22 (chloroform:methanol=9:1);

NMR(CD₃OD): δ 7.69 (d, J=16.2 Hz, 1H), 7.61 (d, J=8.1 Hz, 2H), 7.32-7.24(m) and 7.29 (d, J=8.1 Hz) total 4H, 7.05 (s, 1H), 6.52 (d, J=16.2 Hz,1H), 5.05-4.70 (m, 2H, covered with H₂O in CD₃OD), 3.63-3.50 (m, 2H),2.37 (s, 3H), 2.22 (d, J=0.9 Hz, 3H), 1.65 (m, 1H), 0.93 (d, J=6.3 Hz,6H).

Example 2(61)3-methyl-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamicacid

TLC: Rf 0.37 (chloroform:methanol=9:1);

NMR: δ 7.76 (d, J=16.2 Hz, 1H), 7.47 (d, J=7.8 Hz, 1H), 7.45-7.35 (m,2H), 7.32-7.23 (m, 2H), 7.20 (m, 1H), 6.98 (s, 1H), 6.48 (d, J=16.2 Hz,1H), 5.03-4.82 (m, 2H), 3.70-3.50 (m, 2H), 2.36 (s, 3H), 2.34 (s, 3H),1.74-1.58 (m, 1H), 0.91 (d, J=6.9 Hz, 6H).

Example 2(62)3-chloro-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamicacid

TLC: Rf 0.28 (n-hexane:ethyl acetate=1:2);

NMR: δ 7.71 (d, J=16.2 Hz, 1H), 7.58 (s, 1H), 7.52-7.44 (m, 3H), 7.29(d, J=8.1 Hz, 1H) 7.19 (s, 1H), 7.01 (d, J=0.9 Hz, 1H), 6.50 (d, J=16.2Hz, 1H), 5.02 (br, 2H), 3.62 (d, J=6.6 Hz, 2H), 2.35 (s, 3H), 1.68 (sep,J=6.6 Hz, 1H), 0.93 (d, J=6.6 Hz, 6H).

Example 2(63)3-methyl-4-[2-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid

TLC: Rf 0.20 (n-hexane:ethyl acetate=1:2);

MS (FAB, Pos.): 515(M+H)⁺.

Example 2(64)3-methyl-4-[2-[N-isobutyl-1-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid

TLC: Rf 0.22 (n-hexane:ethyl acetate=1:2);

MS (FAB, Pos.): 529(M+H)⁺.

Example 2(65)4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamicacid

TLC: Rf 0.31 (chloroform:methanol=9:1);

NMR: δ 7.79 (d, J=15.9 Hz, 1H), 7.56 and 7.27 (each d, J=8.1 Hz, each2H), 7.21 (s, 1H), 6.95-6.88 (m, 2H), 6.48 (d, J=15.9 Hz, 1H), 5.00-4.65(m, 2H), 3.72-3.42 (m, 2H), 2.33-2.22 (m, 6H), 1.78-1.60 (m, 1H),1.05-0.83 (m, 6H).

Example 2(66)3-methyl-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamicacid

TLC: Rf 0.30 (chloroform:methanol=9:1);

NMR: δ 7.76 (d, J=16.2 Hz, 1H), 7.42-7.37 (m, 2H), 7.30-7.15 (m, 2H),6.98-6.89 (m, 2H), 6.47 (d, J=16.2 Hz, 1H), 4.95-4.67 (m, 2H), 3.72-3.40(m, 2H), 2.38-2.22 (m, 9H), 1.77-1.61 (m, 1H), 1.05-0.82 (m, 6H).

Example 2(67)3-methyl-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]cinnamicacid

TLC: Rf 0.41 (chloroform:methanol=9:1);

NMR: δ 7.76 (d, J=16.2 Hz, 1H), 7.39 (d, J=8.4 Hz, 1H), 7.38 (s, 1H),7.27 (d, J=8.4 Hz, 1H), 7.23 (s, 1H), 6.97 (s, 1H), 6.81 (s, 1H), 6.47(d, J=16.2 Hz, 1H), 5.04-4.66 (m, 2H), 3.65-3.39 (m, 2H), 2.36 (s, 3H),2.35 (s, 3H), 2.33 (s, 3H), 1.75-1.61 (m, 1H), 0.92 (d, J=6.6 Hz, 6H).

Example 2(68)4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid

TLC: Rf 0.33 (chloroform:methanol=10:1);

MS (APCI, Neg. 20V): 513 (M−H)⁻.

Example 2(69) 3-chloro-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamic acid

TLC: Rf 0.17 (chloroform:methanol=9:1);

NMR(CD₃OD): δ 7.69 (d, J=1.8 Hz, 1H), 7.65 (d, J=15.9 Hz, 1H), 7.59 (dd,J=8.1, 1.5 Hz, 1H), 7.35 (d, J=8.1 Hz, 1H), 7.29 (d, J=1.2 Hz, 1H), 7.04(s, 1H), 6.88 (s, 1H), 6.57 (d, J=15.9 Hz, 1H), 5.10-4.60 (m, 2H),3.63-3.50 (m, 2H), 2.28 (s, 3H), 2.21 (d, J=1.2 Hz) and 2.20 (s) total6H, 1.66 (m, 1H), 1.03-0.85 (m, 6H).

Example 2(70)3-methoxy-4-[2-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid

TLC: Rf 0.40 (dichloromethane:methanol=10:1);

MS (FAB, Pos.): 545 (M+H)⁺.

Example 2(71)4-[6-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.43 (chloroform:methanol=9:1);

NMR: 8.10 (d, J=8.4 Hz, 2H), 7.34 (d, J=8.4 Hz, 2H), 7.16 (s, 1H), 6.89(d, J=0.9 Hz, 1H), 6.76 (s, 1H), 5.06-4.70 (br, 2H), 3.78-3.45 (br, 2H),2.87 (t, J=7.5 Hz, 4H), 2.31 (d, J=0.9 Hz, 3H), 2.09 (m, 2H), 1.74 (m,1H), 1.04-0.86 (br, 6H).

Example 2(72)4-[6-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.42 (chloroform:methanol=9:1);

NMR: δ 7.79 (d, J=15.9 Hz, 1H), 7.55 (d, J=8.1 Hz, 2H), 7.28 (d, J=8.1Hz, 2H), 7.15 (s, 1H), 6.89 (d, J=0.9 Hz, 1H), 6.77 (s, 1H), 6.47 (d,J=15.9 Hz, 1H), 5.05-4.60 (br, 2H), 3.78-3.45 (br, 2H), 2.86 (t, J=7.8Hz, 4H), 2.30 (d, J=0.9 Hz, 3H), 2.08 (m, 2H), 1.73 (m, 1H), 1.06-0.83(br, 6H).

Example 2(73)3-methyl-4-[6-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.34 (dichloromethane:methanol=19:1);

NMR: δ 7.95-7.92 (m, 2H), 7.31 (d, J=7.8 Hz, 1H), 7.16 (s, 1H), 6.91(brs, 1H), 6.79 (s, 1H), 4.93 (brs, 1H), 4.73 (brs, 1H), 3.75-3.45 (m,2H), 2.92-2.84 (m, 4H), 2.34 (s, 3H), 2.31 (d, J=0.6 Hz, 3H), 2.10 (m,2H), 1.74 (m, 1H), 1.08-0.80 (brs, 6H).

Example 2(74)3-methyl-4-[6-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.32 (dichloromethane:methanol=19:1);

NMR: δ 7.76 (d, J=15.9 Hz, 1H), 7.40-7.36 (m, 2H), 7.25 (m, 1H), 7.14(s, 1H), 6.91 (brs, 1H), 6.80 (s, 1H), 6.46 (d, J=15.9 Hz, 1H), 4.90(brs, 1H), 4.69 (brs, 1H), 3.75-3.43 (m, 2H), 2.95-2.80 (m, 4H), 2.31(s, 6H), 2.09 (m, 2H), 1.72 (m, 1H), 1.05-0.85 (brs, 6H).

Example 2(75)4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamicacid

TLC: Rf 0.37 (chloroform:methanol=9:1);

NMR(CD₃OD): δ 8.39 (ddd, J=4.5, 1.5, 0.9 Hz, 1H), 7.82 (dt, J=7.5, 1.5Hz, 1H), 7.72-7.64 (m, 2H), 7.60 (d, J=8.1 Hz, 2H), 7.53 (d, J=7.5 Hz,1H), 7.38 (ddd, J=7.5, 4.5, 0.9 Hz, 1H), 7.34-7.22 (m, 4H), 6.54 (d,J=15.9 Hz, 1H), 4.95-4.78 (m, 2H), 3.61 (d, J=6.6 Hz, 2H), 1.60 (m, 1H),0.91 (d, J=6.9 Hz, 6H).

Example 2(76)4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoicacid

TLC: Rf 0.27 (chloroform:methanol=9:1);

NMR(CD₃OD): δ 8.63 (m, 1H), 8.53 (dd, J=5.1, 1.8 Hz, 1H), 7.99 (d, J=8.4Hz) and 7.94 (m) total 3H, 7.56 (d, J=7.5 Hz, 1H), 7.40-7.29 (m, 3H),7.23 (d, J=8.4 Hz, 2H), 5.10-4.80 (m, 2H), 3.58-3.40 (m, 2H), 1.61 (m,1H), 0.92 (brd, J=6 Hz, 6H).

Example 2(77)3-chloro-4-[2-[N-isopropyl-N-(2-pyridylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid

TLC: Rf 0.43 (chloroform:methanol=9:1);

NMR(CD₃OD): δ 8.63 (m, 1H), 8.02 (d, J=1.8 Hz, 1H), 7.98-7.84 (m, 3H),7.70 (d, J=8.1 Hz, 1H), 7.50 (m, 1H), 7.11 (s, 1H), 7.09 (s, 1H), 5.16(ABd, J=13.5 Hz) and 5.08 (ABd, J=13.5 Hz) total 2H, 4.61 (sept, J=6.6Hz, 1H), 2.39 (3, 3H), 1.12 (d, J=6.6 Hz) and 1.10 (d, J=6.6 Hz) total6H.

Example 2(78)3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid

TLC: Rf 0.37 (chloroform:methanol=10:1);

NMR: δ 8.52 (m, 1H), 7.94-7.92 (m, 2H), 7.77-7.68 (m, 2H), 7.31-7.24 (m,3H), 6.76 (s, 1H), 4.83 (brs, 2H), 3.65-3.50 (m, 2H), 2.34 (s, 6H), 1.66(m, 1H), 0.91 (d, J=6.6 Hz, 6H).

Example 2(79)3-methyl-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid

TLC: Rf 0.16 (dichloromethane:methanol=20:1);

NMR: δ 12.90 (s, 1H), 8.67 (d, J=1.8 Hz, 1H), 8.62 (dd, J=4.8, 1.8 Hz,1H), 7.94 (dt, J=8.1, 1.8 Hz, 1H), 7.74 (s, 1H), 7.68 (d, J=8.1 Hz, 1H),7.37 (dd, J=8.1, 4.8 Hz, 1H), 7.27 (s, 1H), 7.24 (s, 1H), 7.01 (d, J=8.1Hz, 1H), 4.95 (br, 1H), 4.76 (br, 1H), 3.45-3.30 (m, 2H), 2.34 (s, 3H),2.24 (s, 3H), 1.49 (sept, J=6.6 Hz, 1H), 0.90-0.70 (br, 6H).

Example 2(80)3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid

TLC: Rf 0.40 (chloroform:methanol=9:1);

NMR: δ 8.50-8.40 (m, 1H), 7.95-7.85 (m, 2H), 7.75-7.60 (m, 2H),7.30-7.20 (m, 3H), 6.89 (s, 1H), 4.76 (br, 2H), 3.61 (br, 2H), 2.31 (s,3H), 2.29 (s, 3H), 1.75-1.55 (m, 1H), 1.00-0.80 (m, 6H).

Example 2(81)4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid

TLC: Rf 0.31 (chloroform:methanol=9:1);

NMR: δ 8.83 (d, J=2.4, 0.6 Hz, 1H), 8.61 (dd, J=5.1, 1.8 Hz, 1H), 8.10(d, J=8.4 Hz, 2H), 7.78-7.71 (m, 1H), 7.36 (s, 1H), 7.29-7.22 (m, 1H),7.08 (d, J=8.4 Hz, 2H), 6.90 (s, 1H), 4.94-4.72 and 4.50-4.25 (each m,each 1H), 3.75-3.56 and 3.45-3.24 (each m, each 1H), 2.36 (s, 3H),1.79-1.63 (m, 1H), 1.16-0.80 (m, 6H).

Example 2(82)3-chloro-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid

TLC: Rf 0.29 (chloroform:methanol=9:1);

NMR: δ 8.87 (d, J=1.8 Hz, 1H), 8.63 (dd, J=5.1, 1.8 Hz, 1H), 8.13 (d,J=1.8 Hz, 1H), 8.03 (dd, J=8.1, 1.8 Hz, 1H), 7.73-7.66 (m, 1H), 7.40 (s,1H), 7.36 (dd, J=8.1, 5.1 Hz, 1H), 7.05 (d, J=8.1 Hz, 1H), 6.96 (s, 1H),4.92-4.74 and 4.54-4.34 (each m, each 1H), 3.72-3.63 and 3.50-3.33 (eachm, each 1H), 2.39 (s, 3H), 1.84-1.68 (m, 1H), 1.20-0.92 (m, 6H).

Example 2(83)3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamicacid

TLC: Rf 0.32 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 12.39 (br s, 1H, 8.51 (d, J=4.5 Hz, 1H), 7.90 (dd,J=7.5, 7.5 Hz, 1H), 7.70 (d, J=7.5 Hz, 1H), 7.55 (d, J=16.0 Hz, 1H),7.53-7.46 (m, 5H), 7.35 (d, J=8.0 Hz, 1H), 7.14 (d, J=8.0 Hz, 1H), 6.55(d, J=16.0 Hz, 1H), 5.00 (br s, 2M, 3.49 (d, J=7.0 Hz, 2H), 2.25 (s,3H), 1.45 (triple septet, J=7.0, 7.0 Hz, 1H), 0.78 (d, J=7.0 Hz, 6H).

Example 2(84)3-methoxy-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.38 (chloroform:methanol=9:1);

NMR: δ 8.47 (d, J=4.8 Hz, 1H), 7.75-7.60 (m, 3H), 7.56 (d, J=1.5 Hz,1H), 7.20-7.15 (m, 2H), 7.12 (s, 1H), 6.65 (s, 1H), 4.84 (br, 1H), 4.66(br, 1H), 3.92 (s, 3H), 3.61 (br, 2H), 2.22 (s, 3H), 2.18 (s, 3H),1.80-1.60 (m, 1H), 0.96 (br, 6H).

Example 2(85)3-methoxy-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.35 (chloroform:methanol=9:1);

NMR: δ 8.86 (dd, J=2.1, 0.9 Hz, 1H), 8.57 (dd, J=5.1, 1.5 Hz, 1H),7.75-7.65 (m, 2H), 7.61 (d, J=1.5 Hz, 1H), 7.30-7.20 (m, 2H), 6.92 (d,J=7.8 Hz, 1H), 6.72 (s, 1H), 4.75 (d, J=12.3 Hz, 1H), 4.43 (d, J=12.3Hz, 1H), 3.93 (s, 3H), 3.75-3.60 (m, 1H), 3.45-3.35 (m, 1H), 2.29 (s,3H), 2.25 (s, 3H), 1.85-1.65 (m, 1H), 1.09 (d, J=6.3 Hz, 3H), 0.92 (d,J=6.3 Hz, 3H).

Example 2(86)3-methyl-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.61 (chloroform:methanol:water=8:2:0.2);

NMR(DMSO-d₆): δ 12.87 (brs, 1H), 8.64 (d, J=1.8 Hz, 1H), 8.59 (dd,J=4.8, 1.8 Hz, 1H), 7.91 (dt, J=8.1, 1.8 Hz, 1H), 7.73 (s, 1H), 7.67 (d,J=8.1 Hz, 1H), 7.35 (dd, J=8.1, 4.8 Hz, 1H), 7.04-6.96 (m, 3H), 4.92(br, 1H), 4.66 (br, 1H), 3.48-3.22 (br, 2H), 2.23 (s, 3H), 2.22 (s, 3H),2.15 (s, 3H), 1.49 (sep, J=6.9 Hz, 1H), 0.98-0.75 (m, 6H).

Example 2(87)3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.66 (chloroform:methanol:water=8:2:0.2);

NMR(DMSO-d₆): δ 12.88 (s, 1H), 8.47 (d, J=4.5 Hz, 1H), 7.87 (dt, J=1.5,7.8 Hz, 1H), 7.75 (s, 1H), 7.71 (d, J=7.8 Hz, 1H), 7.63 (d, J=7.8 Hz,1H), 7.42 (ddd, J=7.8, 4.5, 1.5 Hz, 1H), 7.16 (d, J=7.8 Hz, 1H), 6.93(s, 1H), 6.91 (s, 1H), 4.80 (br, 2H), 3.57 (d, J=6.6 Hz, 2H), 2.25 (s,3H), 2.18 (s, 3H), 2.09 (s, 3H), 1.49 (sept, J=6.6 Hz, 1H), 0.81 (d,J=6.6 Hz, 6H).

Example 2(88)3-methyl-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid

TLC: Rf 0.31 (chloroform:methanol=9:1);

NMR: δ 8.83 (d, J=1.8 Hz, 1H), 8.61 (dd, J=5.4, 1.8 Hz, 1H), 7.93 (d,J=8.1 Hz, 1H), 7.92 (s, 1H), 7.78 (dt, J=8.1, 1.8 Hz 1H), 7.34 (s, 1H),7.23 (dd, J=8.1, 5.4 Hz, 1H), 6.95 (d, J=8.1 Hz, 1H), 6.94 (s, 1H),4.88-4.65 and 4.54-4.34 (each m, each 1H), 3.71-3.53 and 3.43-3.24 (eachm, each 1H), 2.36 (s, 3H), 2.27 (s, 3H), 1.78-1.63 (m, 1H), 1.08-0.79(m, 6H).

Example 2(89)4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.33 (chloroform:methanol=10:1);

NMR: δ 8.46 (m, 1H), 8.09-8.05 (m, 2H), 7.71-7.60 (m, 2H), 7.28-7.25 (m,2H), 7.20 (m, 1H), 7.09 (s, 1H), 6.62 (s, 1H), 5.02-4.50 (m, 2H),3.83-3.43 (m, 2H), 2.21 (s, 3H), 2.17 (s, 3H), 1.67 (m, 1H), 1.04-0.82(m, 6H).

Example 2(90)4-[2-[N-isopropyl-N-(2-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamicacid

TLC: Rf 0.44 (chloroform:methanol=9:1);

NMR: δ 8.70-8.60 (m, 1H), 7.84 (d, J=7.5 Hz, 1H), 7.79 (d, J=15.9 Hz,1H), 7.71 (dt, J=1.8, 7.5 Hz, 1H), 7.55 (d, J=8.4 Hz, 2H), 7.39 (d,J=8.4 Hz, 2H), 7.35-7.25 (m, 1H), 6.99 (s, 1H), 6.96 (s, 1H), 6.48 (d,J=15.9 Hz, 1H), 4.96 (d, J=12.3 Hz, 1H), 4.92 (d, J=12.3 Hz, 1H),4.75-4.60 (m, 1H), 2.26 (s, 3H), 1.14 (d, J=6.9 Hz, 3H), 1.11 (d, J=6.9Hz, 3H).

Example 2(91)3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamicacid

TLC: Rf 0.37 (chloroform:methanol=9:1);

NMR: δ 8.50-8.40 (m, 1H), 7.77 (d, J=15.9 Hz, 1H), 7.75-7.60 (m, 2H),7.40-7.35 (m, 2H), 7.25-7.20 (m, 2H), 7.15 (d, J=8.4 Hz, 1H), 6.90 (s,1H), 6.49 (d, J=15.9 Hz, 1H), 4.73 (br, 2H), 3.60 (br, 2H), 2.29 (s,3H), 2.28 (s, 3H), 1.70-1.55 (m, 1H), 0.91 (d, J=6.6 Hz, 6H).

Example 2(92)3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid

TLC: Rf 0.36 (dichloromethane:methanol=20:1);

MS (FAB, Pos.): 509 (M+H)⁺.

Example 2(93)4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid

TLC: Rf 0.27 (chloroform:methanol=10:1);

MS (APCI, Neg. 20V): 493 (M−H)⁻.

Example 2(94)3-methyl-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid

TLC: Rf 0.33 (dichloromethane:methanol=20:1);

MS (FAB, Pos.): 509 (M+H)⁺.

Example 2(95)3-chloro-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid

TLC: Rf 0.43 (chloroform:methanol=3:1);

NMR: δ 8.88-8.82 (m, 1H), 8.61-8.52 (m, 1H), 7.75-7.68 (m, 1H), 7.61 (d,J=15.9 Hz, 1H), 7.52 (d, J=1.5 Hz, 1H), 7.47 (d, J=8.1 Hz, 1H),7.32-7.20 (m, 2H), 6.97 (d, J=8.1 Hz, 1H), 6.70 (s, 1H), 6.50 (d, J=15.9Hz, 1H), 4.88-4.75 and 4.53-4.41 (each m, each 1H), 3.74-3.58 and3.48-3.32 (each m, each 1H), 2.29 and 2.25 (each s, each 3H), 1.82-1.63(m, 1H), 1.15-0.82 (m, 6H).

Example 2(96)3-methyl-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]cinnamicacid

TLC: Rf 0.36 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 8.65 (m, 2H), 7.94 (m, 1H), 7.54 (d, J=16.2 Hz) and 7.51(s) total 2H, 7.43 (d, J=8.1 Hz, 1H), 7.38 (dd, J=8.1, 4.8 Hz, 1H), 7.26(s, 1H), 7.22 (s, 1H), 6.98 (d, J=8.1 Hz, 1H), 6.53 (d, J=16.2 Hz, 1H),5.00-4.85 (m, 2H), 3.48-3.10 (m, 2H, covered with H₂O in DMSO-d₆), 2.34(s, 3H), 2.21 (s, 3H), 1.48 (m, 1H), 0.93 (m, 6H).

Example 2(97)3-chloro-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamicacid

TLC: Rf 0.25 (chloroform:methanol=10:1);

MS (APCI, Neg. 20V): 567 (M−H)⁻.

Example 2(98)3-methyl-4-[6-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.45 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.79 (s, 1H), 7.75 (d, J=8.0 Hz, 1H), 7.59 (d, J=8.0 Hz,1H), 7.11 (s, 1H), 6.90 (d, J=3.3 Hz, 1H), 6.82 (s, 1H), 6.30-6.20 (m,1H), 5.08 (s, 2H), 4.30-4.20 (m, 1H), 2.87 (t, J=7.5 Hz, 2H), 2.79 (t,J=7.5 Hz, 2H), 2.35 (s, 3H), 2.28 (s, 3H), 2.10-1.95 (m, 2H), 0.97 (d,J=6.6 Hz, 6H).

Example 2(99)3-methyl-4-[6-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.50 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.60-7.50 (m, 4H), 7.11 (s, 1H), 6.89 (d, J=3.3 Hz, 1H),6.80 (s, 1H), 6.52 (d, J=16.2 Hz, 1H), 6.30-6.20 (m, 1H), 5.04 (d,J=13.5 Hz, 1H), 5.01 (d, J=13.5 Hz, 1H), 4.30-4.20 (m, 1H), 2.87 (t,J=7.2 Hz, 2H), 2.78 (t, J=7.2 Hz, 2H), 2.32 (s, 3H), 2.28 (s, 3H),2.10-1.95 (m, 2H), 0.97 (d, J=6.6 Hz, 6H).

Example 2(100)4-[6-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.42 (chloroform:methanol=9:1);

NMR: δ 7.79 (d, J=16.2 Hz, 1H), 7.57 (d, J=8.4 Hz, 2H), 7.51 (d, J=8.4Hz, 2H), 6.89 (s, 1H), 6.84 (s, 1H), 6.80 (d, J=3.3 Hz, 1H), 6.46 (d,J=16.2 Hz, 1H), 6.02 (m, 1H), 5.14-5.00 (m, 2H), 4.46 (m, 1H), 2.91-2.80(m, 4H), 2.31 (s, 3H), 2.14-2.02 (m, 2H), 1.11 (d, J=6.6 Hz, 3H), 1.10(d, J=6.6 Hz, 3H).

Example 2(101)3-methyl-4-[2-[N-(2-methyl-2-propenyl)-N-(4-methyl-2-thiazolylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid

TLC: Rf 0.44 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.79 (s, 1H), 7.77 (d, J=8.4 Hz, 1H), 7.57 (s, 1H), 7.28(d, J=8.4 Hz, 1H), 7.27 (s, 1H), 7.23 (s, 1H), 4.97 (m, 2H), 4.77 (m,1H), 4.72 (m, 1H), 4.21 (m, 2H), 2.34 (s, 3H), 2.32 (s, 3H), 2.22 (s,3H), 1.68 (s, 3H).

Example 2(102)4-[2-[N-(2-methyl-2-propenyl)-N-(4-methyl-2-thiazolylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamicacid

TLC: Rf 0.43 (chloroform:methanol=9:1);

NMR: δ 7.80 (d, J=15.9 Hz, 1H), 7.58 (d, J=8.4 Hz, 2H), 7.45 (d, J=8.1Hz, 1H), 7.33 (d, J=8.4 Hz, 2H), 7.30-7.20 (m, 1H), 7.15 (s, 1H), 6.99(s, 1H), 6.50 (d, J=15.9 Hz, 1H), 4.97 (s, 2H), 4.77 (s, 1H), 4.72 (s,1H), 4.37 (s, 2H), 2.35 (s, 3H), 1.77 (s, 3H).

Example 2(103)3-methyl-4-[2-[N-(2-methyl-2-propenyl)-N-(4-methyl-2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.24 (dichloromethane:methanol=19:1);

NMR(DMSO-d₆): δ 7.77-7.73 (m, 2H), 7.50 (brs, 1H), 7.23 (d, J=6.9 Hz,1H), 6.99 (s, 1H), 6.96 (s, 1H), 4.87 (brs, 2H), 4.74 (brs, 1H), 4.71(brs, 1H), 4.20 (brs, 2H), 2.28 (s, 3H), 2.19 (s, 3H), 2.16 (d, J=0.6Hz, 3H), 2.11 (s, 3H), 1.68 (s, 3H).

Example 2(104)3-methyl-4-[6-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.43 (chloroform:methanol=9:1);

NMR: δ 7.96 (d, J=8.1 Hz, 1H), 7.93 (s, 1H), 7.89 (d, J=3.0 Hz, 1H),7.58 (d, J=8.1 Hz, 1H), 7.46 (d, J=3.0 Hz, 1H), 6.95 (s, 1H), 6.86 (s,1H), 5.05 and 4.99 (each d, J=13.5 Hz, each 1H), 4.69 (sept, J=6.6 Hz,1H), 2.94-2.79 (m, 4H), 2.39 (s, 3H), 2.16-2.02 (m, 2H), 1.18 and 1.15(each d, J=6.6 Hz, each 3H).

Example 2(105)3-methyl-4-[6-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.41 (chloroform:methanol=9:1);

NMR: δ 7.93 (d, J=8.4 Hz, 1H), 7.92 (s, 1H), 7.71 (d, J=3.0 Hz, 1H),7.35 (d, J=3.0 Hz, 1H), 7.31 (d, J=8.4 Hz, 1H), 7.15 (s, 1H), 6.77 (s,1H), 5.02-4.64 (m, 2H), 3.81-3.43 (m, 2H), 2.95-2.76 (m, 4H), 2.34 (s,3H), 2.17-2.01 (m, 2H), 1.82-1.64 (m, 1H), 1.08-0.83 (m, 6H).

Example 2(106)3-methyl-4-[6-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.34 (dichloromethane:methanol=19:1);

NMR: δ 7.97 (d, J=8.1 Hz, 1H), 7.94 (s, 1H), 7.57 (d, J=8.1 Hz, 1H),7.00 (brs, 1H), 6.94 (s, 1H), 6.86 (s, 1H), 5.05 (d, J=13.5 Hz, 1H),4.99 (d, J=13.5 Hz, 1H), 4.70 (m, 1H), 2.92-2.81 (m, 4H), 2.47 (s, 3H),2.39 (s, 3H), 2.09 (m, 2H), 1.18 (d, J=6.6 Hz, 3H), 1.15 (d, J=6.6 Hz,3H).

Example 2(107)4-[6-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.37 (chloroform:methanol=10:1);

NMR: δ 8.13 (d, J=8.1 Hz, 2H), 7.88 (d, J=3.3 Hz, 1H), 7.51 (d, J=8.1Hz, 2H), 7.44 (d, J=3.3 Hz, 1H), 6.95 (s, 1H), 6.84 (s, 1H), 5.06 (d,J=13.5 Hz, 1H), 5.05 (d, J=13.5 Hz, 1H), 4.71 (m, 1H), 2.92-2.78 (m,4H), 2.14-2.02 (m, 2H), 1.18 (d, J=6.6 Hz, 3H), 1.16 (d, J=6.6 Hz, 3H).

Example 2(108)4-[6-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.35 (chloroform:methanol=10:1);

NMR: δ 8.11 (d, J=8.1 Hz, 2H), 7.71 (d, J=3.3 Hz, 1H), 7.35 (d, J=3.3Hz, 1H), 7.34 (d, J=8.1 Hz, 2H), 7.15 (s, 1H), 6.75 (s, 1H), 4.97 (m,1H), 4.77 (m, 1H), 3.80-3.47 (m, 2H), 2.89-2.82 (m, 4H), 2.15-2.01 (m,2H), 1.73 (m, 1H), 1.05-0.85 (m, 6H).

Example 2(109)4-[6-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.41 (chloroform:methanol=9:1);

NMR: δ 8.11 (d, J=8.4 Hz, 2H), 7.50 (d, J=8.4 Hz, 2H), 6.98 (d, J=0.9Hz, 1H), 6.94 (s, 1H), 6.84 (s, 1H), 5.11-5.00 (m, 2H), 4.71 (m, 1H),2.91-2.79 (m, 4H), 2.47 (d, J=0.9 Hz, 3H), 2.15-2.03 (m, 2H), 1.18 (d,J=6.6 Hz, 3H), 1.15 (d, J=6.6 Hz, 3H).

Example 2(110)4-[6-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.40 (chloroform:methanol=9:1);

NMR: δ 7.79 (d, J=15.9 Hz, 1H), 7.56 (d, J=8.4 Hz, 2H), 7.45 (d, J=8.4Hz, 2H), 6.98 (d, J=0.6 Hz, 1H), 6.92 (s, 1H), 6.85 (s, 1H), 6.47 (d,J=15.9 Hz, 1H), 5.06-4.95 (m, 2H), 4.70 (m, 1H), 2.92-2.78 (m, 4H), 2.46(d, J=0.6 Hz, 3H), 2.16-2.01 (m, 2H), 1.17 (d, J=6.6 Hz, 3H), 1.14 (d,J=6.6 Hz, 3H).

Example 2(111) 3-methyl-4-[6-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamic acid

TLC: Rf 0.30 (dichloromethane:methanol=19:1);

NMR(DMSO-d₆): δ 12.38 (brs, 1H), 7.57 (brs, 1H), 7.56 (d, J=15.9 Hz,1H), 7.53 (s, 1H), 7.49 (brd, J=8.1 Hz, 1H), 7.39 (d, J=8.1 Hz, 1H),7.13 (s, 1H), 6.83 (s, 1H), 6.53 (d, J=15.9 Hz, 1H), 4.99 (brs, 2H),4.47 (m, 1H), 2.87 (m, 2H), 2.77 (m, 2H), 2.37 (d, J=0.9 Hz, 3H), 2.30(s, 3H), 2.02 (m, 2H), 1.04 (d, J=6.6 Hz, 3H), 1.00 (d, J=6.6 Hz, 3H).

Example 2(112)4-[2-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.57 (chloroform:methanol=9:1);

NMR: δ 8.10 (d, J=8.1 Hz, 2H), 7.86 (d, J=3.0 Hz, 1H), 7.49 (d, J=8.1Hz, 2H), 7.43 (d, J=3.0 Hz, 1H), 6.85 (s, 1H), 6.75 (s, 1H), 5.04 (s,2H), 4.72 (sept, J=6.9 Hz, 1H), 2.23 (s, 3H), 2.15 (s, 3H), 1.19 (d,J=6.9 Hz, 3H), 1.15 (d, J=6.9 Hz, 3H).

Example 2(113)4-[2-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.56 (chloroform:methanol=9:1);

NMR: δ 8.11 (d, J=8.4 Hz, 2H), 7.70 (d, J=3.0 Hz, 1H), 7.36-7.32 (m,3H), 7.07 (s, 1H), 6.66 (s, 1H), 5.10-4.65 (m, 2H), 3.80-3.45 (m, 2H),2.22 (s, 3H), 2.18 (s, 3H), 1.71 (sept, J=6.9 Hz, 1H), 1.15-0.95 (m,6H).

Example 2(114)4-[2-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid

TLC: Rf 0.56 (chloroform:methanol=9:1);

NMR: δ 7.86 (d, J=3.0 Hz, 1H), 7.79 (d, J=15.9 Hz, 1H), 7.56 (d, J=8.4Hz, 2H), 7.42 (d, J=8.4 Hz, 2H), 7.42 (d, J=3.0 Hz, 1H), 6.84 (s, 1H),6.76 (s, 1H), 6.46 (d, J=15.9 Hz, 1H), 5.04 (d, J=11.7 Hz, 1H), 4.98 (d,J=11.7 Hz, 1H), 4.71 (sept, J=6.6 Hz, H), 2.23 (s, 3H), 2.13 (s, 3H),1.18 (d, J=6.6 Hz, 3H), 1.15 (d, J=6.6 Hz, 3H).

Example 2(115)4-[2-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid

TLC: Rf 0.58 (chloroform:methanol=9:1);

NMR: δ 7.79 (d, J=15.9 Hz, 1H), 7.67 (d, J=3.0 Hz, 1H), 7.55 (d, J=8.4Hz, 2H), 7.34 (d, J=3.0 Hz, 1H), 7.27 (d, J=8.4 Hz, 2H), 7.05 (s, 1H),6.67 (s, 1H), 6.47 (d, J=15.9 Hz, 1H), 5.00-4.62 (m, 2H), 3.80-3.45 (m,2H), 2.22 (s, 3H), 2.17 (s, 3H), 1.70 (sept, J=6.6 Hz, 1H), 1.10-0.96(m, 6H).

Example 2(116)4-[6-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.39 (chloroform:methanol=10:1);

NMR: δ 7.87 (d, J=3.3 Hz, 1H), 7.80 (d, J=15.9 Hz, 1H), 7.56 (d, J=7.8Hz, 2H), 7.45 (d, J=7.8 Hz, 2H), 7.44 (d, J=3.3 Hz, 1H), 6.94 (s, 1H),6.85 (s, 1H), 6.48 (d, J=15.9 Hz, 1H), 5.01 (d, J=13.2 Hz, 1H), 5.00 (d,J=13.2 Hz, 1H), 4.70 (m, 1H), 2.91-2.79 (m, 4H), 2.14-2.01 (m, 2H), 1.17(d, J=6.6 Hz, 3H), 1.15 (d, J=6.6 Hz, 3H).

Example 2(117)4-[6-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.40 (chloroform:methanol=10:1);

NMR: δ 7.80 (d, J=15.9 Hz, 1H), 7.69 (d, J=3.3 Hz, 1H), 7.55 (d, J=8.4Hz, 2H), 7.34 (d, J=3.3 Hz, 1H), 7.27 (d, J=8.4 Hz, 2H), 7.14 (s, 1H),6.75 (s, 1H), 6.48 (d, J=15.9 Hz, 1H), 4.92 (m, 1H), 4.70 (m, 1H),3.78-3.46 (m, 2H), 2.90-2.80 (m, 4H), 2.14-2.01 (m, 2H), 1.72 (m, 1H),1.02-0.83 (m, 6H).

Example 2(118)3-methyl-4-[2-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.27 (chloroform:methanol=9:1);

NMR: δ 8.00-7.90 (m, 2H), 7.87 (d, J=3.0 Hz, 1H), 7.55 (d, J=7.8 Hz,1H), 7.44 (d, J=3.0 Hz, 1H), 6.85 and 6.77 (each s, each 1H), 5.09-4.92(m, 2H), 4.78-4.62 (m, 1H), 2.39 (s, 3H), 2.25 (s, 3H), 2.16 (s, 3H),1.19 and 1.15 (each d, J=6.6 Hz, each 3H).

Example 2(119)3-methyl-4-[2-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.27 (chloroform:methanol=9:1);

NMR: δ 7.95-7.89 (m, 2H), 7.70 and 7.34 (each d, J=3.3 Hz, each 1H),7.32-7.29 (m, 1H), 7.06 and 6.69 (each s, each 1H), 5.00-4.68 (m, 2H),3.78-3.48 (m, 2H), 2.34 (s, 3H), 2.23 (s, 3H), 2.18 (s, 3H), 1.80-1.65(m, 1H), 1.08-0.82 (m, 6H).

Example 2(120)3-methyl-4-[2-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid

TLC: Rf 0.25 (chloroform:methanol=9:1);

NMR: δ 7.87 (d, J=3.0 Hz, 1H), 7.77 (d, J=16.2 Hz, 1H), 7.52-7.32 (m,4H), 6.83 and 6.79 (each s, each 1H), 6.46 (d, J=16.2 Hz, 1H), 5.05-4.87(m, 2H), 4.75-4.62 (m, 1H), 2.36 (s, 3H), 2.25 (s, 3H), 2.15 (s, 3H),1.17 and 1.13 (each d, J=6.6 Hz, each 3H).

Example 2(121)3-methyl-4-[2-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid

TLC: Rf 0.25 (chloroform:methanol=9:1);

NMR: δ 7.76 (d, J=16.2 Hz, 1H), 7.69 (d, J=3.0 Hz, 1H), 7.42-7.35 (m,2H), 7.34 (d, J=3.0 Hz, 1H), 7.25-7.19 (m, 1H), 7.05 and 6.70 (each s,each 1H), 6.47 (d, J=16.2 Hz, 1H), 4.95-4.62 (m, 2H), 3.75-3.48 (m, 2H),2.31 (s, 3H), 2.24 (s, 3H), 2.18 (s, 3H), 1.78-1.62 (m, 1H), 1.78-1.62(m, 6H).

Example 2(122)3-methyl-4-[6-[N-isopropyl-N-(2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.44 (chloroform:methanol=9:1);

NMR: δ 7.88 (d, J=3.0 Hz, 1H), 7.77 (d, J=16.2 Hz, 1H), 7.51 (d, J=8.1Hz, 1H), 7.45 (d, J=3.0 Hz, 1H), 7.42 (d, J=8.1 Hz, 1H), 7.38 (s, 1H),6.93 (s, 1H), 6.87 (s, 1H), 6.46 (d, J=16.2 Hz, 1H), 5.02 and 4.95 (eachd, J=12.9 Hz, each 1H), 4.68 (sept, J=6.6 Hz, 1H), 2.94-2.78 (m, 4H),2.36 (s, 3H), 2.16-2.02 (m, 2H), 1.17 and 1.14 (each d, J=6.6 Hz, each3H).

Example 2(123)3-methyl-4-[6-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.39 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.98 (d, J=3.0 Hz, 1H), 7.87 (d, J=3.0 Hz, 1H), 7.56 (d,J=16.2 Hz, 1H), 7.52 (s, 1H), 7.50 (d, J=8.1 Hz, 1H), 7.18 (d, J=8.1 Hz,1H), 7.06 (s, 1H), 7.00 (s, 1H), 6.54 (d, J=16.2 Hz, 1H), 5.04-4.66 (m,2H), 3.57-3.37 (m, 2H), 2.93-2.68 (m, 4H), 2.27 (s, 3H), 2.11-1.93 (m,2H), 1.64-1.46 (m, 1H), 0.94-0.74 (m, 6H).

Example 2(124) 4-[3-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-2-naphthyloxymethyl]benzoic acid

TLC: Rf 0.33 (chloroform:methanol=9:1);

NMR(CD₃OD): δ 8.05 (d, J=8.4 Hz, 2H), 7.82-7.75 (m, 3H), 7.53 (d, J=8.4Hz, 2H), 7.51-7.35 (m, 3H), 6.71 (d, J=3.3 Hz, 1H), 6.05 (m, 1H),5.42-4.95 (br, 2H), 3.62 (d, J=7.5 Hz, 2H), 2.13 (s, 3H), 1.79-1.61 (,1H), 0.94 (d, J=6.3 Hz, 6H).

Reference Example 4N-[4,5-dimethyl-2-(2-methyl-4-cyanophenylmethyloxy)phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide

Under atmosphere of argon, a solution of3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid prepared in Example 2 (178 mg) in dichloromethane (1.5 ml) wascooled to 0° C., then oxalyl chloride (48 μl) and a catalytic amount ofN,N-dimethylformamide was added thereto. After the solution was stirredfor 1 hour at room temperature, the reaction mixture was concentratedunder reduced pressure, and azeotroped with toluene. Under atmosphere ofargon, the residue was dissolved in dichloromethane (1.5 ml), and cooledto 0° C. The solution was added by 28% aqueous ammonia (1 ml) andstirred for 5 minutes. The solution was added by water and ethylacetate. The organic layer was washed, dried and concentrated underreduced pressure. Under atmosphere of argon, the residue was dissolvedin dichloromethane (1.5 ml), and cooled to 0° C. The solution was addedby pyridine (0.18 ml) and trifluoromethanesulfonic acid anhydride (0.12ml) and stirred for 50 minutes. The reaction mixture was poured intowater, then it was added by ethyl acetate. The organic layer was washed,dried and concentrated under reduced pressure. The residue was purifiedby column chromatography on silica gel (hexane-ethyl acetate) to givethe title compound (149 mg) having the following physical data.

TLC: Rf 0.74 (n-hexane:ethyl acetate=1:1).

Example 3N-[4,5-dimethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide

ToN-[4,5-dimethyl-2-(2-methyl-4-cyanophenylmethyloxy)phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamideprepared in Reference Example 4 (79 mg), trimethyltin azide (43 mg) wasadded, and mixture was refluxed for 7 hours, then stirred for 1 day atroom temperature. The reaction mixture was added by methanol (3 ml) and2N hydrochloric acid (2 ml), then stirred for 2 hours. The solution wasadded by water and ethyl acetate. The organic layer was washed, driedand concentrated under reduced pressure. The residue was washed byhexane-ethyl acetate to give the title compound (81 mg) having thefollowing physical data.

TLC: Rf 0.52 (chloroform:methanol:water=8:2:0.2);

MS (FAB, Pos.): 510 (M+H)⁺.

Example 3(1) to Example 3(38)

By the same procedures as described in Reference Examples 1 to 3 andExample 3, the title compounds having the following physical data wereobtained.

Example 3(1)N-[4-chloro-5-methyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide

TLC: Rf 0.40 (dichloromethane:methanol=10:1);

MS (FAB, Pos.): 530 (M)⁺.

Example 3(2)N-[4,5-dimethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(5-methyl-2-furyl)sulfonylamide

TLC: Rf 0.52 (chloroform:methanol:water=8:2:0.2);

MS (FAB, Pos.): 496 (M+H)⁺.

Example 3(3)N-[4-chloro-5-methyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide

TLC: Rf 0.39 (chloroform:methanol:water=8:2:0.2);

NMR: δ 8.05 (d, J=8.1 Hz, 2H), 7.47 (d, J=8.1 Hz, 2H), 7.08 (s, 1H),6.93 (s, 1H), 6.80 (d, J=3.3 Hz, 1H), 6.01 (m, 1H), 5.15-4.80 (br, 2H),3.46 (d, J=7.2 Hz, 2H), 2.27 (s, 3H), 2.19 (s, 3H), 1.64 (m, 1H), 0.88(d, J=6.9 Hz, 6H).

Example 3(4)N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(5-methyl-2-furyl)sulfonylamide

TLC: Rf 0.41 (chloroform:methanol:water=8:2:0.2);

NMR(DMSO-d₆): δ 8.04 (d, J=8.1 Hz, 2H), 7.66 (d, J=8.1 Hz, 2H), 7.01 (s,1H), 6.91 (d, J=3.3 Hz, 1H), 6.76 (s, 1H), 6.29-6.23 (m, 1H), 5.18 and5.12 (each d, J=13.5 Hz, each 1H), 4.30 (sept, J=6.6 Hz, 1H), 2.30 (s,3H), 2.23 (s, 3H), 2.14 (s, 3H), 1.02 and 1.00 (each d, J=6.6 Hz, each3H).

Example 3(5)N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide

TLC: Rf 0.37 (chloroform:methanol:water=8:2:0.2);

NMR(DMSO-d₆): δ 8.04 (d, J=8.4 Hz, 2H), 7.53 (d, J=8.4 Hz, 2H), 6.96 (s,1H), 6.92 (s, 1H), 6.82 (d, J=3.3 Hz, 1H), 6.19-6.13 (m, 1H), 5.28-4.82(m, 2H), 3.38 (d, J=6.9 Hz, 2H), 2.21 (s, 3H), 2.14 (s, 6H), 1.64-1.44(m, 1H), 0.85 (d, J=6.6 Hz, 6H).

Example 3(6)N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-thiazolylsulfonylamide

TLC: Rf 0.46 (chloroform:methanol:water=8:2:0.2);

NMR: δ 8.09 (d, J=8.4 Hz, 2H), 7.76 (d, J=2.7 Hz, 1H), 7.49-7.44 (m,4H), 7.27 (m, 1H), 7.19 (s, 1H), 5.01 (br, 2H), 3.63 (d, J=7.2 Hz, 2H),1.67 (m, 1H), 0.97 (d, J=7.2 Hz, 6H).

Example 3(7)N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-2-thiazolylsulfonylamide

TLC: Rf 0.31 (chloroform:methanol:water=8:2:0.2);

NMR: δ 8.07 (d, J=8.1 Hz, 2H), 7.94 (d, J=3.3 Hz, 1H), 7.60 (d, J=8.1Hz, 2H), 7.56 (d, J=3.3 Hz, 1H), 7.36-7.20 (m, 3H), 5.17 and 5.13 (eachd, J=12.0 Hz, each 1H), 4.68 (sept, J=6.6 Hz, 1H), 1.15 and 1.14 (eachd, J=6.6 Hz, each 3H).

Example 3(8)N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.31 (chloroform:methanol:water=8:2:0.2);

NMR: δ 8.04 (d, J=8.1 Hz, 2H), 7.42 (d, J=8.1 Hz, 1H), 7.37 (d, J=8.1Hz, 2H), 7.23 (m, 1H), 7.16 (s, 1H), 6.99 (s, 1H), 4.95 (br, 2H), 3.56(d, J=6.6 Hz, 2H), 2.26 (s, 3H), 1.59 (sept, J=6.6 Hz, 1H), 0.84 (d,J=6.6 Hz, 6H).

Example 3(9)N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.42 (chloroform:methanol:water=8:2:0.2);

NMR: δ 7.93 (d, J=8.1 Hz, 2H), 7.41 (d, J=8.1 Hz, 2H), 7.24-7.16 (m,3H), 7.02 (s, 1H), 5.10-4.92 (m, 2H), 4.57 (quint, J=6.6 Hz, 1H), 2.39(s, 3H), 1.04 (d, J=6.6 Hz, 3H), 1.02 (d, J=6.6 Hz, 3H).

Example 3(10)N-[4-chloro-5-methyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.24 (dichloromethane:methanol=10:1);

MS (FAB, Pos.): 547 (M)⁺.

Example 3(11)N-[4-chloro-5-methyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.24 (dichloromethane:methanol=10:1);

MS (FAB, Pos.): 533 (M)⁺.

Example 3(12)N-[4-trifluoromethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.38 (chloroform:methanol:water=8:2:0.2);

NMR: δ 7.91 (s, 1H), 7.82 (d, J=7.8 Hz, 1H), 7.64 (d, J=7.8 Hz, 1H),7.33-7.20 (m, 3H), 7.12 (s, 1H), 5.11 (s, 2H), 4.65 (sept, J=6.6 Hz,1H), 2.49 (s, 3H), 2.43 (s, 3H), 1.12 (d, J=6.6 Hz, 6H).

Example 3(13)N-[4-trifluoromethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.34 (chloroform:methanol:water=8:2:0.2);

NMR: δ 7.97 (s, 1H), 7.89 (d, J=8.1 Hz, 1H), 7.48-7.38 (m, 2H),7.34-7.18 (m, 2H), 7.05 (s, 1H), 5.12-4.84 (m, 2H), 3.59 (d, J=7.2 Hz,2H), 2.41 (s, 3H), 2.34 (s, 3H), 1.74-1.58 (m, 1H), 0.89 (d, J=6.6 Hz,6H).

Example 3(14)N-[4,5-dimethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.46 (chloroform:methanol:water=8:2:0.2);

MS (FAB, Pos.): 527 (M+H)⁺.

Example 3(15)N-[4,5-dimethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.52 (chloroform:methanol:water=8:2:0.2);

MS (FAB, Pos.): 513 (M+H)⁺.

Example 3(16)N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.29 (chloroform:methanol=5:1);

MS (APCI, Neg. 20V): 497 (M−H)⁻.

Example 3(17)N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.26 (chloroform:methanol=5:1);

MS (APCI, Neg. 20V): 511 (M−H)⁻.

Example 3(18)N-[4-chloro-5-methyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.31 (chloroform:methanol:water=8:2:0.2);

NMR: δ 8.02 (d, f=8.4 Hz, 2H), 7.51 (d, J=8.4 Hz, 2H), 7.10 (s, 1H),6.98 (s, 2H), 5.03 and 4.95 (each d, J=12.6 Hz, each 1H), 4.65 (sept,J=6.6 Hz, 1H), 2.46 (s, 3H), 2.26 (s, 3H), 1.13 and 1.12 (each d, J=6.6Hz, each 3H).

Example 3(19)N-[4-chloro-5-methyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.29 (chloroform:methanol:water=8:2:0.2);

NMR(DMSO-d₆): δ 8.05 (d, J=8.4 Hz, 2H), 7.52 (s, 1H), 7.45 (d, J=8.4 Hz,2H), 7.26 (s, 1H), 7.25 (s, 1H), 5.25-4.73 (m, 2H), 3.62-3.40 (m, 2H),2.26 (s, 3H), 2.22 (s, 3H), 1.66-1.50 (m, 1H), 0.88 (d, J=6.6 Hz, 6H).

Example 3(20)N-[4,5-dimethyl-2-[2-methoxy-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.31 (chloroform:methanol=5:1);

NMR(CDCl₃+1 drop of CD₃OD) δ 7.71 (d, J=7.5 Hz, 1H), 7.70 (d, J=1.5 Hz,1H), 7.51 (dd, J=7.5, 1.5 Hz, 1H), 7.07 (d, J=0.9 Hz, 1H), 6.83 (s, 1H),6.82 (s, 1H), 5.09 (d, J=13.8 Hz, 1H), 5.04 (d, J=13.8 Hz, 1H), 4.68 (m,1H), 3.97 (s, 3H), 2.46 (d, J=0.9 Hz, 3H), 2.25 (s, 3H), 2.16 (s, 3H),1.15 (d, J=6.6 Hz, 3H), 1.14 (d, J=6.6 Hz, 3H).

Example 3(21)N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-3-pyridylsulfonylamide

TLC: Rf 0.47 (chloroform:methanol=3:1);

NMR(DMSO-d₆): δ 8.91 (dd, J=2.4, 0.6 Hz, 1H), 8.73 (dd, J=4.5, 1.8 Hz,1H), 8.14 (ddd, J=8.4, 2.4, 1.8 Hz, 1H), 8.04 (d, J=8.4 Hz, 2H), 7.57(s, 1H), 7.55 (d, J=8.4 Hz, 2H), 7.47 (ddd, J=8.4, 4.5, 0.6 Hz, 1H),7.43-7.38 (m, 2H), 5.28 (d, J=12.3 Hz, 1H), 5.21 (d, J=12.3 Hz, 1H),4.45-4.25 (m, 1H), 1.04 (d, J=6.6 Hz, 3H), 1.00 (d, J=6.6 Hz, 3H).

Example 3(22)N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide

TLC: Rf 0.47 (chloroform:methanol=3:1);

NMR: δ 8.89 (d, J=1.5 Hz, 1H), 8.46 (dd, J=4.8, 1.5 Hz, 1H), 8.00 (d,J=8.4 Hz, 2H), 7.83 (dt, J=8.1, 1.5 Hz, 1H), 7.59 (d, J=8.4 Hz, 1H),7.35 (dd, J=8.4, 0.9 Hz, 1H), 7.26-7.20 (m, 1H), 7.19 (d, J=0.9 Hz, 1H),7.14 (d, J=8.4 Hz, 2H), 4.95 (brs, 1H), 4.77 (brs, 1H), 3.56 (brs, 1H),3.40 (brs, 1H), 1.70-1.60 (m, 1H), 0.94 (brs, 6H).

Example 3(23)N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide

TLC: Rf 0.47 (chloroform:methanol=3:1);

NMR: δ 8.69 (d, J=4.8 Hz, 1H), 8.02 (d, J=8.4 Hz, 2H), 7.92-7.76 (m,2H), 7.52 (d, J=8.4 Hz, 2H), 7.46-7.38 (m, 1H), 7.30-7.26 (m, 3H), 5.08(d, J=12.0 Hz, 1H), 5.01 (d, J=12.0 Hz, 1H), 4.75-4.55 (m, 1H), 1.11 (d,J=7.5 Hz, 3H), 1.08 (d, J=7.5 Hz, 3H).

Example 3(24)N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide

TLC: Rf 0.38 (chloroform:methanol=3:1);

NMR: δ 8.60-8.45 (m, 1H), 8.10 (d, J=8.4 Hz, 2H), 7.80-7.70 (m, 2H),7.49 (d, J=8.1 Hz, 1H), 7.38 (d, J=8.4 Hz, 2H), 7.38-7.31 (m, 1H),7.30-7.20 (m, 1H), 7.14 (d, J=1.8 Hz, 1H), 4.91 (brs, 2H), 3.63 (brd,J=6.3 Hz, 2H), 1.70-1.55 (m, 1H), 0.89 (d, J=6.6 Hz, 6H).

Example 3(25)N-[4-trifluoromethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide

TLC: Rf 0.24 (chloroform:methanol=3:1);

NMR: δ 8.69 (d, J=4.8 Hz, 1H), 7.92-7.75 (m, 4H), 7.58 (d, J=7.8 Hz,1H), 7.48-7.39 (m, 1H), 7.31-7.18 (m, 3H), 5.03 (s, 2H), 4.72-4.58 (m,1H), 2.37 (s, 3H), 1.11 and 1.09 (each d, J=6.6 Hz, each 3H).

Example 3(26)N-[4,5-dimethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide

TLC: Rf 0.40 (chloroform:methanol:water=8:2:0.2);

MS (FAB, Pos.): 507 (M+H)⁺.

Example 3(27)N-[4,5-dimethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide

TLC: Rf 0.44 (chloroform:methanol:water=8:2:0.2);

MS (FAB, Pos.): 507 (M+H)⁺.

Example 3(28)N-[4-chloro-5-methyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide

TLC: Rf 0.28 (chloroform:methanol:water=8:2:0.2);

NMR(DMSO-d₆): δ 8.69 (d, J=1.8 Hz, 1H), 8.64 (dd, J=4.8, 1.8 Hz, 1H),8.00 (d, J=8.1 Hz, 2H), 7.98-7.92 (m, 1H), 7.40 (dd, J=8.1, 4.8 Hz, 1H),7.30 (d, J=8.4 Hz, 2H), 7.27 (s, 1H), 7.24 (s, 1H), 5.17-4.68 (m, 2H),3.46-3.16 (m, 2H), 2.28 (s, 3H), 1.60-1.42 (m, 1H), 1.00-0.73 (m, 6H).

Example 3(29)N-[4,5-dimethyl-2-[2-chloro-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide

TLC: Rf 0.22 (chloroform:methanol:water=40:10:1);

NMR: δ 8.52 (d, J=4.5 Hz, 1H), 8.20 (d, J=1.5 Hz, 1H), 7.98 (d, J=7.8Hz, 1H), 7.79 (dt, J=1.5, 8.1 Hz, 1H), 7.71 (d, J=8.1 Hz, 1H), 7.47 (d,J=7.8 Hz, 1H), 7.35-7.30 (m, 1H), 7.04 (s, 1H), 6.63 (s, 1H), 4.90 (br,1H), 4.64 (br, 1H), 3.67 (br, 1H), 3.57 (br, 1H), 2.21 (s, 3H), 2.15 (s,3H), 1.80-1.60 (m, 1H), 0.91 (br, 6H).

Example 3(30)N-[4,5-dimethyl-2-[2-chloro-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-3-pyridylsulfonylamide

TLC: Rf 0.22 (chloroform:methanol:water=40:10:1);

NMR: δ 9.11 (d, J=1.8 Hz, 1H), 8.61 (dd, J=4.8, 1.5 Hz, 1H), 8.20-8.10(m, 2H), 7.88 (dd, J=7.8, 1.5 Hz, 1H), 7.42 (dd, J=8.1, 4.8 Hz, 1H),7.33 (d, J=7.8 Hz, 1H), 7.01 (s, 1H), 6.79 (s, 1H), 4.96 (d, J=13.5 Hz,1H), 4.93 (d, J=13.5 Hz, 1H), 4.60-4.45 (m, 1H), 2.29 (s, 3H), 2.23 (s,3H), 1.25 (d, J=6.6 Hz, 3H), 1.11 (d, J=6.6 Hz, 3H).

Example 3(31)N-[4,5-dimethyl-2-[2-chloro-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide

TLC: Rf 0.22 (chloroform:methanol:water=40:10:1);

NMR: δ 8.97 (d, J=1.8 Hz, 1H), 8.55-8.45 (m, 1H), 8.15 (d, J=1.5 Hz,1H), 7.89 (d, J=7.8 Hz, 1H), 7.83 (dt, J=8.1, 1.8 Hz, 1H), 7.31 (dd,J=8.1, 4.8 Hz, 1H), 7.24 (s, 1H), 7.07 (d, J=7.8 Hz, 1H), 6.75 (s, 1H),4.89 (d, J=12.5 Hz, 1H), 4.63 (d, J=12.5 Hz, 1H), 3.70-3.60 (m, 1H),3.45-3.30 (m, 1H), 2.30 (s, 3H), 2.26 (s, 3H), 1.80-1.60 (m, 1H), J=6.6Hz, 3H), 0.93 (d, J=6.6 Hz, 3H).

Example 3(32)N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide

TLC: Rf 0.23 (chloroform:methanol=5:1);

MS (APCI, Neg. 20V): 477 (M−H)⁻.

Example 3(33)N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide

TLC: Rf 0.23 (chloroform:methanol=5:1);

MS (APCI, Neg. 20V): 491 (M−H)⁻.

Example 3(34)N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide

TLC: Rf 0.23 (chloroform:methanol=5:1);

MS (APCI, Neg. 20V): 491 (M−H)⁻.

Example 3(35)N-[4-chloro-5-methyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide

TLC: Rf 0.30 (chloroform:methanol:water=8:2:0.2);

NMR(DMSO-d₆): δ 8.67 (d, J=3.6 Hz, 1H), 7.98-7.88 (m, 2H), 7.85-7.78 (m,2H), 7.55-7.48 (m, 2H), 7.37 (s, 1H), 7.04 (s, 1H), 5.10 (ABd, J=13.2Hz) and 5.04 (ABd, J=13.2 Hz) total 2H, 4.49 (sept, J=6.9 Hz, 1H), 2.36(s, 3H), 2.23 (s, 3H), 1.02 (d, J=6.9 Hz) and 0.99 (d, J=6.9 Hz) total6H.

Example 3(36)N-[4-chloro-5-methyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide

TLC: Rf 0.26 (chloroform:methanol:water=8:2:0.2);

NMR(DMSO-d₆): δ 8.48 (m, 1H), 7.93-7.85 (m) and 7.90 (dd, J=7.8, 1.8 Hz)total 2H, 7.81 (d, J=8.1 Hz, 1H), 7.68 (d, J=8.1 Hz, 1H), 7.44 (ddd,J=7.8, 4.8, 1.2 Hz, 1H), 7.29 (s) and 7.27 (d, J=7.8 Hz) total 2H, 7.20(s, 1H), 4.92 (m, 2H), 3.47 (m, 2H), 2.31 (s, 3H), 2.23 (s, 3H), 1.50(m, 1H), 0.81 (d, J=6.6 Hz, 6H).

Example 3(37)N-[4,5-dimethyl-2-[2-methoxy-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide

TLC: Rf 0.23 (dichloromethane:methanol=10:1);

MS (FAB, Pos.): 523 (M+H)⁺.

Example 3(38)N-[4,5-dimethyl-2-[2-methoxy-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide

TLC: Rf 0.23 (chloroform:methanol=10:1);

Reference Example 5N-[4,5-dimethyl-2-[2-methyl-4-(N-hydroxyamidino)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide

To a solution ofN-[4,5-dimethyl-2-(2-methyl-4-cyanophenylmethyloxy)phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamideprepared in Reference Example 4 (70 mg) in ethanol (2 ml), triethylamine(42 μl) and hydroxylamine hydrogen chloride salt (21 mg) were added atroom temperature, then mixture was refluxed for 5 hours. Aftertermination of reaction, the reaction mixture was poured into ethylacetate-water. The organic layer was washed, dried and concentratedunder reduced pressure to give the title compound (80 mg) having thefollowing physical data.

TLC: Rf 0.38 (n-hexane:ethyl acetate=2:3).

Example 4N-[4,5-dimethyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide

To a solution ofN-[4,5-dimethyl-2-[2-methyl-4-(N-hydroxyamidino)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamideprepared in Reference Example 5 (78 mg) in N,N-dimethylformamide (1 ml),pyridine (16 μl) and chloro formic acid 2-ethylhexyl ester (30 μl) wereadded and the mixture was stirred for 1 hour at 0° C. After terminationof reaction, the reaction mixture was poured into ethyl acetate-water.The organic layer was washed, dried and concentrated under reducedpressure. To the residue, xylenes (2 ml) were added, and the mixture wasrefluxed for 6 hours at 140° C. After termination of reaction, thereaction mixture was concentrated under reduced pressure. The residuewas purified by column chromatography on silica gel (hexane-ethylacetate) to give the title compound (42 mg) having the followingphysical data.

TLC: Rf 0.43 (chloroform:methanol=19:1);

NMR: δ 10.69 (br, 1H), 7.62 (s, 1H), 7.59 (d, J=8.1 Hz, 1H), 7.54 (d,J=8.1 Hz, 1H), 6.97 (s, 1H), 6.78 (d, J=3.3 Hz, 1H), 6.71 (s, 1H), 6.00(d, J=3.3 Hz, 1H), 4.94 (br, 2H), 3.46 (d, J=7.5 Hz, 2H), 2.39 (s, 3H),2.24 (s, 3H), 2.19 (s, 3H), 2.18 (s, 3H), 1.70-1.55 (m, 1H), 0.89 (d,J=6.6 Hz, 6H).

Example 4(1) to Example 4(22)

By the same procedures as described in Reference Examples 1 to 5 andExample 4, the compounds having the following physical data wereobtained.

Example 4(1)N-[4-chloro-5-methyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-(5-methyl-2-furyl)sulfonylamide

TLC: Rf 0.40 (chloroform:methanol=19:1);

NMR: δ 10.81 (br, 1H), 7.79 (d, J=8.3 Hz, 2H), 7.63 (d, J=8.3 Hz, 2H),6.97 (s, 1H), 6.92 (s, 1H), 6.84 (d, J=3.3 Hz, 1H), 6.10-6.00 (m, 1H),5.07 (s, 2H), 4.55-4.35 (m, 1H), 2.34 (s, 3H), 2.28 (s, 3H), 1.10 (d,J=6.6 Hz, 3H), 1.07 (d, J=6.6 Hz, 3H).

Example 4(2)N-[4-chloro-5-methyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide

TLC: Rf 0.38 (chloroform:methanol=19:1);

NMR: δ 11.01 (br, 1H), 7.80 (d, J=8.3 Hz, 2H), 7.52 (d, J=8.3 Hz, 2H),7.10 (s, 1H), 6.92 (s, 1H), 6.78 (d, J=3.3 Hz, 1H), 6.05-5.95 (m, 1H),5.02 (br, 2H), 3.45 (d, J=7.2 Hz, 2H), 2.29 (s, 3H), 2.20 (s, 3H),1.70-1.55 (m, 1H), 0.90 (d, J=6.9 Hz, 6H).

Example 4(3)N-[4,5-dimethyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-(5-methyl-2-furyl)sulfonylamide

TLC: Rf 0.43 (chloroform:methanol=19:1);

NMR: δ 10.34 (br, 1H), 7.71 (d, J=8.1 Hz, 1H), 7.65-7.55 (m, 2H), 6.86(d, J=3.3 Hz, 1H), 6.79 (s, 1H), 6.74 (s, 1H), 6.10-6.05 (m, 1H), 4.93(s, 2H), 4.50-4.40 (m, 1H), 2.37 (s, 3H), 2.34 (s, 3H), 2.26 (s, 3H),2.17 (s, 3H), 1.09 (d, J=6.6 Hz, 3H), 1.07 (d, J=6.6 Hz, 3H).

Example 4(4)N-[4,5-dimethyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide

TLC: Rf 0.53 (chloroform:methanol=9:1);

NMR: δ 11.10-10.50 (br, 1H, NH), 7.78 (d, J=8.7 Hz, 2H), 7.52 (d, J=8.7Hz, 2H), 6.97 (s, 1H), 6.78 (d, J=3.3 Hz, 1H), 6.69 (s, 1H), 6.01-5.98(m, 1H), 5.15-4.85 (m, 2H), 3.46 (d, J=7.2 Hz, 2H), 2.22 (s, 3H), 2.20(s, 3H), 2.17 (s, 3H), 1.73-1.60 (m, 1H), 0.90 (d, J=6.9 Hz, 6H).

Example 4(5)N-[4,5-dimethyl-2-[2-methoxy-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide

TLC: Rf 0.46 (dichloromethane:methanol=10:1);

MS (FAB, Pos.): 542 (M+H)⁺.

Example 4(6)N-[4,5-dimethyl-2-[2-methoxy-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-(5-methyl-2-furyl)sulfonylamide

TLC: Rf 0.44 (dichloromethane:methanol=19:1);

NMR: δ 7.68 (d, J=8.1 Hz, 1H), 7.35 (dd, J=8.1, 1.5 Hz, 1H), 7.24 (d,J=1.5 Hz, 1H), 6.91 (d, J=3.3 Hz, 1H), 6.77 (s, 1H), 6.72 (s, 1H), 6.11(dd, J=3.3, 0.6 Hz, 1H), 4.92 (d, J=14.7 Hz, 1H), 4.83 (d, J=14.7 Hz,1H), 4.49 (m, 1H), 3.93 (s, 3H), 2.37 (s, 3H), 2.25 (s, 3H), 2.17 (s,3H), 1.09 (d, J=6.9 Hz, 3H), 1.07 (d, J=6.9 Hz, 3H).

Example 4(7)N-[4-trifluoromethyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-2-thiazolylsulfonylamide

TLC: Rf 0.23 (n-hexane:ethyl acetate=1:1);

NMR: 7.96 (d, J=3.3 Hz, 1H), 7.82 (d, J=8.4 Hz, 2H), 7.65 (d, J=8.4 Hz,2H), 7.57 (d, J=3.3 Hz, 1H), 7.34-7.22 (m, 3H), 5.19 (s, 2H), 4.68(sept, J=6.6 Hz, 1H), 1.15 and 1.14 (each d, J=6.6 Hz, each 3H).

Example 4(8)N-[4-trifluoromethyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.60 (chloroform:methanol:water=8:2:0.2);

NMR: δ 7.82 (d, J=8.4 Hz, 2H), 7.64 (d, J=8.4 Hz, 2H), 7.32-7.24 (m,3H), 7.11 (d, J=0.9 Hz, 1H), 5.19 (s, 2H), 4.68 (quint, J=6.6 Hz, 1H),2.51 (d, J=0.9 Hz, 3H), 1.14 (d, J=6.6 Hz, 6H).

Example 4(9)N-[4-trifluoromethyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.60 (chloroform:methanol:water=8:2:0.2);

NMR: δ 7.83 (d, J=8.4 Hz, 2H), 7.48 (d, J=8.4 Hz, 2H), 7.45 (d, J=7.8Hz, 1H), 7.27 (m, 1H), 7.18 (d, J=1.5 Hz, 1H), 7.04 (d, J=0.6 Hz, 1H),5.05 (br, 2H), 3.60 (d, J=6.9 Hz, 2H), 2.38 (d, J=0.6 Hz, 3H), 1.66(sep, J=6.9 Hz, 1H), 0.92 (d, J=6.9 Hz, 6H).

Example 4(10)N-[4-chloro-5-methyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.37 (chloroform:methanol=19:1);

NMR: δ 10.89 (br, 1H), 7.79 (d, J=8.4 Hz, 2H), 7.44 (d, J=8.4 Hz, 2H),7.17 (s, 1H), 7.01 (s, 1H), 6.92 (s, 1H), 4.99 (br, 1H), 4.87 (br, 1H),3.57 (br, 2H), 2.36 (s, 3H), 2.27 (s, 3H), 1.80-1.60 (m, 1H), 0.93 (d,J=6.6 Hz, 6H).

Example 4(11)N-[4-chloro-5-methyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.43 (ethyl acetate);

NMR(DMSO-d₆): δ 7.67 (s, 1H), 7.64 (d, J=8.1 Hz, 1H), 7.50 (s, 1H), 7.34(s, 1H), 7.32 (d, J=8.1 Hz, 1H), 7.21 (s, 1H), 5.06 (brs, 1H), 4.87(brs, 1H), 3.45 (brs, 2H), 2.33 (s, 3H), 2.27 (s, 3H), 2.22 (s, 3H),1.70-1.50 (m, 1H), 0.86 (brd, J=6.3 Hz, 6H).

Example 4(12)N-[4,5-dimethyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.45 (chloroform:methanol=19:1);

NMR: δ 10.56 (br, 1H), 7.64 (d, J=8.1 Hz, 1H), 7.62 (s, 1H), 7.57 (dd,J=8.1, 1.8 Hz, 1H), 7.07 (s, 1H), 6.83 (s, 1 μl), 6.77 (s, 1H), 4.98 (s,2H), 4.75-4.60 (m, 1H), 2.49 (s, 3H), 2.39 (s, 3H), 2.25 (s, 3H), 2.16(s, 3H), 1.14 (d, J=6.6 Hz, 3H), 1.13 (d, J=6.6 Hz, 3H).

Example 4(13)N-[4,5-dimethyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.45 (chloroform:methanol=19:1);

NMR: δ 10.95 (br, 1H), 7.62 (s, 1H), 7.59 (d, J=8.1 Hz, 1H), 7.40 (d,J=8.1 Hz, 1H), 7.03 (s, 1H), 6.99 (s, 1H), 6.71 (s, 1H), 4.91 (br, 1H),4.82 (br, 1H), 3.57 (br, 2H), 2.37 (s, 3H), 2.34 (s, 3H), 2.24 (s, 3H),2.17 (s, 3H), 1.80-1.60 (m, 1H), 0.93 (br, 6H).

Example 4(14)N-[4,5-dimethyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.42 (chloroform:methanol=10:1);

NMR: δ 7.77 (d, J=8.4 Hz, 2H), 7.57 (d, J=8.4 Hz, 2H), 7.06 (d, J=0.9Hz, 1H), 6.83 (s, 1H), 6.74 (s, 1H), 5.05 (d, J=12.9 Hz, 1H), 5.00 (d,J=12.9 Hz, 1H), 4.68 (m, 1H), 2.49 (d, J=0.9 Hz, 3H), 2.24 (s, 3H), 2.15(s, 3H), 1.15 (d, J=6.6 Hz, 3H), 1.13 (d, J=6.6 Hz, 3H).

Example 4(15)N-[4,5-dimethyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.39 (chloroform:methanol 10:1);

NMR: δ 7.78 (d, J=8.4 Hz, 2H), 7.43 (d, J=8.4 Hz, 2H), 7.03 (s, 1H),6.97 (d, J=0.9 Hz, 1H), 6.68 (s, 1H), 5.12-4.68 (m, 2H), 3.73-3.42 (m,2H), 2.35 (d, J=0.9 Hz, 3H), 2.23 (s, 3H), 2.17 (s, 3H), 1.69 (m, 1H),1.03-0.86 (m, 6H).

Example 4(16)N-[4,5-dimethyl-2-[2-methoxy-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-(4-methyl-2-thiazolyl)sulfonylamide

TLC: Rf 0.37 (dichloromethane:methanol=19:1);

NMR: δ 7.63 (d, J=7.8 Hz, 1H), 7.33 (dd, J=7.8, 1.5 Hz, 1H), 7.30 (d,J=1.5 Hz, 1H), 7.08 (brs, 1H), 6.83 (s, 1H), 6.76 (s, 1H), 5.02 (d,J=14.4 Hz, 1H), 4.93 (d, J=14.4 Hz, 1H), 4.69 (m, 1H), 3.93 (s, 3H),2.49 (d, J=1.2 Hz, 3H), 2.25 (s, 3H), 2.16 (s, 3H), 1.14 (d, J=6.9 Hz,3H), 1.13 (d, J=6.9 Hz, 3H).

Example 4(17)N-[4-trifluoromethyl-2-[4-(5-oxo-1,2,4-thiadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-2-thiazolylsulfonylamide

TLC: Rf 0.44 (n-hexane:ethyl acetate=1:1);

NMR: δ 11.41 (brs, 1H), 7.94 (d, J=8.4 Hz, 2H), 7.94 (d, J=3.0 Hz, 1H),7.60 (d, J=8.4 Hz, 2H), 7.54 (d, J=3.0 Hz, 1H), 7.34-7.20 (m, 3H), 5.16(s, 2H), 4.69 (sept, J=6.6 Hz, 1H), 1.15 (d, J=6.6 Hz, 6H).

Example 4(18)N-[4-trifluoromethyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide

TLC: Rf 0.46 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 8.60-8.50 (m, 1H), 7.90 (dt, J=1.8, 7.8 Hz, 1H), 7.81(d, J=8.4 Hz, 2H), 7.72 (d, J=7.5 Hz, 1H), 7.55-7.35 (m, 6H), 5.08 (brs,2H), 3.52 (brd, J=7.5 Hz, 2H), 1.60-1.40 (m, 1H), 0.83 (d, J=6.6 Hz,6H).

Example 4(19)N-[4,5-dimethyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide

TLC: Rf 0.33 (chloroform:methanol=19:1);

NMR: δ 10.41 (br, 1H), 8.75-8.70 (m, 1H), 7.90 (dd, J=7.8, 0.9 Hz, 1H),7.80 (dt, J=0.9, 7.8 Hz, 1H), 7.65-7.50 (m, 3H), 7.41 (ddd, J=7.8, 4.8,0.9 Hz, 1H), 6.78 (s, 1H), 6.72 (s, 1H), 4.87 (d, J=13.4 Hz, 1H), 4.83(d, J=13.4 Hz, 1H), 4.75-4.60 (m, 1H), 2.34 (s, 3H), 2.25 (s, 3H), 2.13(s, 3H), 1.10 (d, J=6.6 Hz, 6H).

Example 4(20)N-[4,5-dimethyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide

TLC: Rf 0.30 (chloroform:methanol=19:1);

NMR: δ 11.28 (br, 1H), 8.84 (d, J=1.8 Hz, 1H), 8.49 (dd, J=4.8, 1.8 Hz,1H), 7.87 (dt, J=8.1, 1.8 Hz, 1H), 7.62 (s, 1H), 7.47 (d, J=7.8 Hz, 1H),7.19 (dd, J=8.1, 4.8 Hz, 1H), 7.15 (s, 1H), 6.97 (d, J=7.8 Hz, 1H), 6.69(s, 1H), 4.82 (br, 1H), 4.62 (br, 1H), 3.53 (br, 1H), 3.34 (br, 1H),2.30 (s, 3H), 2.27 (s, 3H), 2.22 (s, 3H), 1.80-1.60 (m, 1H), 1.00 (br,3H), 0.87 (br, 3H).

Example 4(21)N-[4,5-dimethyl-2-[2-methoxy-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide

TLC: Rf 0.36 (dichloromethane:methanol=10:1);

MS (FAB, Pos.): 539 (M+H)⁺.

Example 4(22)N-[4,5-dimethyl-2-[2-methoxy-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide

TLC: Rf 0.37 (dichloromethane:methanol=19:1);

NMR: δ 8.73 (ddd, J=4.8, 1.5, 0.9 Hz, 1H), 7.91 (ddd, J=7.8, 1.2, 0.9Hz, 1H), 7.82 (ddd, J=7.8, 7.8, 1.5 Hz, 1H), 7.57 (d, J=7.8 Hz, 1H),7.43 (ddd, J=7.8, 4.8, 1.2 Hz, 1H), 7.32 (dd, J=7.8, 1.5 Hz, 1H), 7.26(m, 1H), 6.76 (s, 1H), 6.72 (s, 1H), 4.88 (d, J=14.1 Hz, 1H), 4.78 (d,J=14.1 Hz, 1H), 4.71 (m, 1H), 3.91 (s, 3H), 2.24 (s, 3H), 2.13 (s, 3H),1.10 (d, J=6.6 Hz, 3H), 1.09 (d, J=6.6 Hz, 3H).

Example 5(1) to Example 5(63)

By the same procedure as described in Reference Examples 1 to 3 andExample 2, the compounds of the present invention having the followingphysical data were obtained.

Example 5(1)3,5-dimethyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoicacid

TLC: Rf 0.49 (chloroform:methanol=10:1);

NMR: δ 7.82 (s, 2H), 7.40-7.20 (m, 3H), 6.70 (d, J=3.3 Hz, 1H),6.00-5.95 (m, 1H), 5.07 (s, 2H), 3.35 (d, J=7.5 Hz, 2H), 2.43 (s, 6H),2.19 (s, 3H), 1.60-1.45 (m, 1H), 0.79 (d, J=6.6 Hz, 6H).

Example 5(2)3-methyl-4-[6-[N-(5-methyl-2-furylsulfonyl)-N-(2-methyl-2-propenyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.54 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.80-7.70 (m, 2H), 7.37 (d, J=7.8 Hz, 1H), 7.05 (s, 1H),6.99 (s, 1H), 6.87 (d, J=3.3 Hz, 1H), 6.17 (d, J=3.3 Hz, 1H), 4.99 (br,2H), 4.72 (s, 2H), 4.13 (br, 2H), 2.83 (t, J=7.4 Hz, 2H), 2.77 (t, J=7.4Hz, 2H), 2.32 (s, 3H), 2.08 (s, 3H), 2.05-1.90 (m, 2H), 1.65 (s, 3H).

Example 5(3)4-[6-[N-cyclopropylmethyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]-3-methylbenzoicacid

TLC: Rf 0.54 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.77 (s, 1H), 7.74 (d, J=8.1 Hz, 1H), 7.38 (d, J=8.1 Hz,1H), 7.09 (s, 1H), 7.02 (s, 1H), 6.85 (d, J=3.3 Hz, 1H), 6.20-6.15 (m,1H), 5.01 (br, 2H), 3.41 (br, 2H), 2.86 (t, J=7.4 Hz, 2H), 2.79 (t,J=7.4 Hz, 2H), 2.32 (s, 3H), 2.10 (s, 3H), 2.10-1.95 (m, 2H), 0.90-0.70(m, 1H), 0.35-0.25 (m, 2H), 0.05-(−0.05) (m, 2H).

Example 5(4)4-[3-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]naphthalen-2-yloxymethyl]benzoicacid

TLC: Rf 0.55 (ethyl acetate:methanol=9:1);

NMR: δ 8.14 (d, J=8.4 Hz, 2H), 7.85 (s, 1H), 7.78 (d, J=8.1 Hz, 1H),7.70 (d, J=8.1 Hz, 1H), 7.51-7.37 (m, 4H), 7.18 (s, 1H), 6.93 (s, 1H),5.17 and 4.96 (each br-m, total 2H), 3.85-3.62 (br-m, 2H), 2.34 (s, 3H),1.82-1.69 (m, 1H), 0.97 (br-s, 6H).

Example 5(5)4-[3-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]naphthalen-2-yloxymethyl]benzoicacid

TLC: Rf 0.55 (ethyl acetate:methanol=9:1);

NMR: δ 8.15 (d, J=8.4 Hz, 2H), 7.72 (d, J=9.0 Hz, 2H), 7.61 (s, 1H),7.60 (d, J=9.0 Hz, 2H), 7.51-7.46 (m, 1H), 7.44-7.35 (m, 1H), 7.24 (s,1H), 7.03 (s, 1H), 5.24 (s, 2H), 4.84-4.75 (m, 1H), 2.52 (s, 3H), 1.26(d, J=6.6 Hz, 3H), 1.17 (d, J=6.6 Hz, 3H).

Example 5(6)4-[3-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]naphthalen-2-yloxymethyl]-3-methylbenzoicacid

TLC: Rf 0.63 (ethyl acetate:methanol=9:1);

NMR: δ 7.98-7.96 (m, 2H), 7.84 (s, 1H), 7.78 (d, J=8.1 Hz, 1H), 7.72 (d,J=8.1 Hz, 1H), 7.52-7.47 (m, 1H), 7.42-7.37 (m, 2H), 7.21 (s, 1H), 6.95(s, 1H), 5.10 and 4.96 (each br-m, total 2H), 3.84-3.60 (br-m, 2H), 2.41(s, 3H), 2.34 (s, 3H), 1.82-1.68 (m, 1H), 0.96 (br-s, 6H).

Example 5(7)4-[3-[N-isopropyl-N-[2-(4-methylthiazolyl)sulfonyl]amino]naphthalen-2-yloxymethyl]-3-methylbenzoicacid

TLC: Rf 0.56 (ethyl acetate:methanol=9:1);

NMR: δ 8.00-7.97 (m, 2H), 7.76-7.65 (m, 3H), 7.61 (s, 1H), 7.52-7.47 (m,1H), 7.40-7.35 (m, 1H), 7.26 (s, 1H), 7.04 (s, 1H), 5.22 (d, J=15.0 Hz,1H), 5.17 (d, J=15.0 Hz, 1H), 4.83-4.73 (m, 1H), 2.53 (s, 3H), 2.46 (s,3H), 1.25 (d, J=6.6 Hz, 3H), 1.16 (d, J=6.6 Hz, 3H).

Example 5(8)4-[3-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]naphthalen-2-yloxymethyl]cinnamicacid

TLC: Rf 0.67 (ethyl acetate:methanol=9:1);

NMR: δ 7.84-7.69 (m, 4H), 7.58 (d, J=8.1 Hz, 2H), 7.51-7.45 (m, 1H),7.41-7.35 (m, 3H), 7.18 (s, 1H), 6.93 (s, 1H), 6.49 (d, J=16.2 Hz, 1H),5.02 and 4.91 (each br-m, total 2H), 3.84-3.62 (br-m, 2H), 2.33 (s, 3H),1.82-1.68 (m, 1H), 0.91 (br-s, 6H).

Example 5(9)4-[3-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]naphthalen-2-yloxymethyl]cinnamicacid

TLC: Rf 0.61 (ethyl acetate:methanol=9:1);

NMR: δ 7.80 (d, J=16.9 Hz, 1H), 7.71 (d, J=8.7 Hz, 2H), 7.61-7.46 (m,6H), 7.39-7.34 (m, 1H), 7.24 (s, 1H), 7.03 (s, 1H), 6.48 (d, J=16.9 Hz,1H), 5.19 (s, 2H), 4.85-4.72 (m, 1H), 2.51 (s, 3H), 1.25 (d, J=6.6 Hz,3H), 1.16 (d, J=6.6 Hz, 3H).

Example 5(10)3-methyl-4-[6-[N-methyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.58 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.77 (s, 1H), 7.74 (d, J=7.8 Hz, 1H), 7.36 (d, J=7.8 Hz,1H), 7.09 (s, 1H), 6.99 (s, 1H), 6.90 (d, J=3.3 Hz, 1H), 6.25-6.15 (m,1H), 5.02 (s, 2H), 3.15 (s, 3H), 2.84 (t, J=7.4 Hz, 2H), 2.78 (t, J=7.4Hz, 2H), 2.32 (s, 3H), 2.12 (s, 3H), 2.10-1.95 (m, 2H).

Example 5(11)4-[6-[N-ethyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]-3-methylbenzoicacid

TLC: Rf 0.59 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.77 (s, 1H), 7.74 (d, J=7.8 Hz, 1H), 7.38 (d, J=7.8 Hz,1H), 7.10 (s, 1H), 6.95 (s, 1H), 6.86 (d, J=3.3 Hz, 1H), 6.16 (d, J=3.3Hz, 1H), 5.01 (br, 2H), 3.58 (br, 2H), 2.86 (t, J=7.4 Hz, 2H), 2.79 (t,J=7.4 Hz, 2H), 2.32 (s, 3H), 2.10 (s, 3H), 2.10-1.95 (m, 2H), 0.99 (t,J=7.2 Hz, 3H).

Example 5(12)4-[6-[N-methyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.53 (chloroform:methanol=9:1);

NMR: δ 7.77 (d, J=15.9 Hz, 1H), 7.55 (d, J=8.4 Hz, 2H), 7.37 (d, J=8.4Hz, 2H), 7.14 (s, 1H), 6.80 (s, 1H), 6.79 (d, J=3.6 Hz, 1H), 6.47 (d,J=15.9 Hz, 1H), 5.97 (d, J=3.6 Hz, 1H), 4.98 (s, 2H), 3.31 (s, 3H),2.90-2.80 (m, 4H), 2.17 (s, 3H), 2.08 (quint, J=7.5 Hz, 2H).

Example 5(13)4-[6-[N-ethyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.53 (chloroform:methanol=9:1);

NMR: δ 7.77 (d, J=16.2 Hz, 1H), 7.55 (d, J=8.4 Hz, 2H), 7.37 (d, J=8.4Hz, 2H), 7.08 (s, 1H), 6.80 (s, 1H), 6.75 (d, J=3.3 Hz, 1H), 6.47 (d,J=16.2 Hz, 1H), 5.94 (d, J=3.3 Hz, 1H), 4.97 (s, 2H), 3.82-3.65 (m, 2H),2.90-2.80 (m, 4H), 2.15 (s, 3H), 2.08 (quint, J=7.2 Hz, 2H), 1.14 (t,J=7.2 Hz, 3H).

Example 5(14)4-[6-[N-(5-methyl-2-furylsulfonyl)-N-propylamino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.54 (chloroform:methanol=9:1);

NMR: δ 7.78 (d, J=15.9 Hz, 1H), 7.55 (d, J=8.1 Hz, 2H), 7.37 (d, J=8.1Hz, 2H), 7.08 (s, 1H), 6.79 (s, 1H), 6.74 (d, J=3.3 Hz, 1H), 6.46 (d,J=15.9 Hz, 1H), 5.94 (brd, J=3.3 Hz, 1H), 4.97 (br s, 2H), 3.65-3.61 (m,2H), 2.90-2.80 (m, 4H), 2.15 (s, 3H), 2.08 (quint, J=7.5 Hz, 2H), 1.53(sext, J=7.2 Hz, 2H), 0.89 (t, J=7.2 Hz, 3H).

Example 5(15)4-[4,5-dimethyl-2-[N-(5-methyl-2-furylsulfonyl)-N-(2-methyl-2-propenyl)amino]phenoxymethyl]-3-methylbenzoicacid

TLC: Rf 0.45 (chloroform:methanol=9:1);

NMR: δ 8.00-7.93 (m, 2H), 7.44 (d, J=8.1 Hz, 1H), 7.02 (s, 1H), 6.75 (d,J=3.3 Hz, 1H), 6.69 (s, 1H), 5.96 (m, 1H), 4.94 (s, 2H), 4.77 (s, 2H),4.27 (s, 2H), 2.38 (s, 3H), 2.22 (s, 3H), 2.18 (s, 3H), 2.12 (s, 3H),1.78 (s, 3H).

Example 5(16)4-[6-[N-(5-methyl-2-furylsulfonyl)-N-(2-methyl-2-propenyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.61 (chloroform:methanol=9:1);

NMR: δ 7.78 (d, J=15.9 Hz, 1H), 7.56 (d, J=8.4 Hz, 2H), 7.36 (d, J=8.4Hz, 2H), 7.09 (s, 1H), 6.76 (s, 1H), 6.74 (d, J=3.0 Hz, 1H), 6.47 (d,J=15.9 Hz, 1H), 5.94 (d, J=3.0 Hz, 1H), 4.95 (brs, 2H), 4.77 (s, 2H),4.38-4.18 (m, 2H), 2.90-2.75 (m, 4H), 2.14 (s, 3H), 2.07 (quint, J=7.5Hz, 2H), 1.78 (s, 3H).

Example 5(17)4-[6-[N-cyclopropylmethyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.51 (chloroform:methanol=9:1);

NMR: δ 7.79 (d, J=15.9 Hz, 1H), 7.55 (d, J=8.4 Hz, 2H), 7.38 (d, J=8.4Hz, 2H), 7.15 (s, 1H), 6.79 (s, 1H), 6.74 (d, J=3.3 Hz, 1H), 6.47 (d,J=15.9 Hz, 1H), 5.94 (d, J=3.3 Hz, 1H), 4.97 (brs, 2H), 3.65-3.50 (m,2H), 2.92-2.70 (m, 4H), 2.15 (s, 3H), 2.08 (quint, J=7.5 Hz, 2H),1.00-0.85 (m, 1H), 0.45-0.36 (m, 2H), 0.20-0.05 (m, 2H).

Example 5(18)4-[6-[N-(5-methyl-2-furylsulfonyl)-N-(2-propenyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.57 (chloroform:methanol=9:1);

NMR: δ 7.79 (d, J=15.9 Hz, 1H), 7.56 (d, J=8.4 Hz, 2H), 7.38 (d, J=8.4Hz, 2H), 7.07 (s, 1H), 6.78 (s, 1H), 6.76 (d, J=3.3 Hz, 1H), 6.47 (d,J=15.9 Hz, 1H), 5.96 (d, J=3.3 Hz, 1H), 5.96-5.77 (m, 1H), 5.13-5.03 (m,2H), 4.97 (s, 2H), 4.42-4.20 (m, 2H), 2.90-2.80 (m, 4H), 2.16 (s, 3H),2.07 (quint, J=7.5 Hz, 2H).

Example 5(19)3-methyl-4-[6-[N-(5-methyl-2-furylsulfonyl)-N-propylamino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.40 (chloroform:methanol=10:1);

NMR: δ 7.95 (d, J=7.8 Hz, 1H), 7.93 (s, 1H), 7.46 (d, J=7.8 Hz, 1H),7.10 (s, 1H), 6.81 (s, 1H), 6.75 (d, J=3.3 Hz, 1H), 5.95 (dd, J=3.3, 0.9Hz, 1H), 4.96 (s, 2H), 3.76-3.47 (m, 2H), 2.92-2.82 (m, 4H), 2.37 (s,3H), 2.13 (s, 3H), 2.15-2.03 (m, 2H), 1.60-1.47 (m, 2H), 0.89 (t, J=7.5Hz, 3H).

Example 5(20)3-methyl-4-[6-[N-(5-methyl-2-furylsulfonyl)-N-(2-propenyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.41 (chloroform:methanol=10:1);

NMR: 7.95 (d, J=7.8 Hz, 1H), 7.94 (s, 1H), 7.47 (d, J=7.8 Hz, 1H), 7.08(s, 1H), 6.80 (s, 1H), 6.78 (d, J=3.3 Hz, 1H), 5.97 (d, J=3.3 Hz, 1H),5.85 (m, 1H), 5.10 (dd, J=16.8, 1.2 Hz, 1H), 5.05 (dd, J=9.9, 1.2 Hz,1H), 4.97 (s, 2H), 4.43-4.18 (m, 2H), 2.91-2.81 (m, 4H), 2.37 (s, 3H),2.15 (s, 3H), 2.13-2.03 (m, 2H).

Example 5(21)4-[4,5-dimethyl-2-[N-methyl-N-(4-methyl-2-thiazolylsulfonyl)amino]phenoxymethyl]-3-methylbenzoicacid

TLC: Rf 0.49 (dichloromethane:methanol=10:1);

NMR: δ 7.94-7.90 (m, 2H), 7.31 (d, J=9.0 Hz, 1H), 7.13 (s, 1H), 6.94 (m,1H), 6.73 (s, 1H), 4.88 (s, 2H), 3.42 (s, 3H), 2.35 (s, 3H), 2.34 (d,J=0.9 Hz, 3H), 2.24 (s, 3H), 2.19 (s, 3H).

Example 5(22)4-[4,5-dimethyl-2-[N-ethyl-N-(4-methyl-2-thiazolylsulfonyl)amino]phenoxymethyl]-3-methylbenzoicacid

TLC: Rf 0.49 (dichloromethane:methanol=10:1);

NMR: δ 7.96-7.90 (m, 2H), 7.32 (d, J=8.1 Hz, 1H), 7.06 (s, 1H), 6.90 (m,1H), 6.74 (s, 1H), 4.87 (brs, 2H), 3.85 (br, 2H), 2.34 (s, 3H), 2.32 (d,J=0.9 Hz, 3H), 2.25 (s, 3H), 2.19 (s, 3H), 1.18 (t, J=7.2 Hz, 3H).

Example 5(23)4-[4,5-dimethyl-2-[N-(4-methyl-2-thiazolylsulfonyl)-N-propylamino]phenoxymethyl]-3-methylbenzoicacid

TLC: Rf 0.49 (dichloromethane:methanol=10:1);

NMR(DMSO-d₆): δ 12.88 (s, 1H), 7.78-7.72 (m, 2H), 7.49 (m, 1H), 7.25 (d,J=7.8 Hz, 1H), 7.03 (s, 1H), 6.95 (s, 1H), 4.88 (br, 2H), 3.59 (br, 2H),2.28 (s, 3H), 2.22 (s, 3H), 2.18 (s, 3H), 2.13 (s, 3H), 1.44-1.35 (m,2H), 0.81 (t, J=7.2 Hz, 3H).

Example 5(24)4-[4,5-dimethyl-2-[N-(4-methyl-2-thiazolylsulfonyl)-N-(2-propenyl)amino]phenoxymethyl]-3-methylbenzoicacid

TLC: Rf 0.49 (dichloromethane:methanol=10:1);

NMR(DMSO-d₆): δ 12.88 (s, 1H), 7.78-7.72 (m, 2H), 7.50 (s, 1H), 7.26 (d,J=7.5 Hz, 1H), 7.01 (s, 1H), 6.95 (s, 1H), 5.74 (m, 1H), 5.09 (d, J=17.1Hz, 1H), 5.04 (d, J=9.9 Hz, 1H), 4.89 (br, 2H), 4.27 (br, 2H), 2.29 (s,3H), 2.21 (s, 3H), 2.18 (s, 3H), 2.12 (s, 3H).

Example 5(25)4-[2-[N-cyclopropylmethyl-N-(4-methyl-2-thiazolylsulfonyl)amino-4,5-dimethyl]phenoxymethyl]-3-methylbenzoicacid

TLC: Rf 0.49 (dichloromethane:methanol=10:1);

NMR(DMSO-d₆): δ 12.87 (br, 1H), 7.78-7.72 (m, 2H), 7.48 (s, 1H), 7.25(d, J=7.5 Hz, 1H), 7.03 (s, 1H), 7.00 (s, 1H), 4.90 (br, 2H), 3.45 (br,2H), 2.27 (s, 3H), 2.23 (s, 3H), 2.17 (s, 3H), 2.14 (s, 3H), 0.82 (m,1H), 0.38-0.30 (m, 2H), 0.10-0.02 (m, 2H).

Example 5(26)4-[4,5-dimethyl-2-[N-(2-hydroxy-2-methylpropyl)-N-(4-methyl-2-thiazolylsulfonyl)amino]phenoxymethyl]-3-methylbenzoicacid

TLC: Rf 0.49 (dichloromethane:methanol=10:1);

NMR: δ 7.99-7.94 (m, 2H), 7.47 (d, J=8.1 Hz, 1H), 7.04 (m, 1H), 6.79 (s,1H), 6.77 (s, 1H), 5.06 (d, J=12.3 Hz, 1H), 4.95 (d, J=12.3 Hz, 1H),3.95 (d, J=15.3 Hz, 1H), 3.73 (d, J=15.3 Hz, 1H), 2.420 (s, 3H), 2.417(s, 3H), 2.23 (s, 3H), 2.11 (s, 3H), 1.25 (s, 3H), 1.21 (s, 3H).

Example 5(27)4-[4,5-dimethyl-2-[N-methyl-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]benzoicacid

TLC: Rf 0.46 (chloroform:methanol=9:1);

NMR: δ 8.11 (d, J=8.4 Hz, 2H), 7.42 (d, J=8.4 Hz, 2H), 7.08 (s, 1H),6.79 (d, J=3.3 Hz, 1H), 6.71 (s, 1H), 5.99-5.95 (m, 1H), 5.03 (s, 2H),3.31 (s, 3H), 2.22 (s, 3H), 2.18 (s, 3H), 2.16 (s, 3H).

Example 5(28)4-[4,5-dimethyl-2-[N-ethyl-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]benzoicacid

TLC: Rf 0.41 (chloroform:methanol=9:1);

NMR: δ 8.10 (d, J=8.4 Hz, 2H), 7.43 (d, J=8.4 Hz, 2H), 7.01 (s, 1H),6.76 (d, J=3.3 Hz, 1H), 6.71 (s, 1H), 5.96-5.93 (m, 1H), 5.02 (s, 2H),3.83-3.65 (m, 2H), 2.23 (s, 3H), 2.18 (s, 3H), 2.14 (s, 3H), 1.14 (t,J=7.2 Hz, 3H).

Example 5(29)4-[4,5-dimethyl-2-[N-(5-methyl-2-furylsulfonyl)-N-propylamino]phenoxymethyl]benzoicacid

TLC: Rf 0.43 (chloroform:methanol=9:1);

NMR: δ 8.11 (d, J=8.4 Hz, 2H), 7.43 (d, J=8.4 Hz, 2H), 7.02 (s, 1H),6.74 (d, J=3.0 Hz, 1H), 6.70 (s, 1H), 5.96-5.93 (m, 1H), 5.01 (s, 2H),3.75-3.53 (m, 2H), 2.22 (s, 3H), 2.18 (s, 3H), 2.14 (s, 3H), 1.60-1.46(m, 2H), 0.90 (t, J=7.2 Hz, 3H).

Example 5(30)4-[6-[N-(2-methyl-2-propenyl)-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.36 (dichloromethane:methanol=19:1);

NMR: δ 8.11 (d, J=8.7 Hz, 2H), 7.35 (d, J=8.7 Hz, 2H), 7.14 (s, 1H),6.92 (brs, 1H), 6.74 (s, 1H), 5.10-4.70 (brs, 2H), 4.80 (brs, 2H),4.60-4.20 (brs, 2H), 2.88-2.82 (m, 4H), 2.32 (d, J=0.9 Hz, 3H), 2.07 (m,2H), 1.83 (s, 3H).

Example 5(31)4-[6-[N-(4-methyl-2-thiazolylsulfonyl)-N-(2-propenyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.34 (dichloromethane:methanol=19:1);

NMR: 8.11 (d, J=8.7 Hz, 2H), 7.35 (d, J=8.7 Hz, 2H), 7.13 (s, 1H), 6.93(brs, 1H), 6.76 (s, 1H), 5.89 (ddt, J=17.1, 10.2, 6.3 Hz, 1H), 5.17-5.06(m, 2H), 4.92 (brs, 2H), 4.70-4.10 (brs, 2H), 2.89-2.83 (m, 4H), 2.34(d, J=0.9 Hz, 3H), 2.08 (m, 2H).

Example 5(32)4-[6-[N-cyclopropylmethyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.36 (dichloromethane:methanol=19:1);

NMR: δ 8.10 (d, J=8.7 Hz, 2H), 7.35 (d, J=8.7 Hz, 2H), 7.22 (s, 1H),6.89 (brs, 1H), 6.78 (s, 1H), 5.10-4.70 (m, 2H), 3.90-3.50 (m, 2H),2.90-2.85 (m, 4H), 2.32 (d, J=0.9 Hz, 3H), 2.09 (m, 2H), 1.00 (m, 1H),0.43 (m, 2H), 0.20 (brs, 2H).

Example 5(33)4-[3-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]-3-methylbenzoicacid

TLC: Rf 0.52 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.92-7.80 (m, 3H), 7.77 (d, J=8.1 Hz, 1H), 7.69 (d,J=8.1 Hz, 1H), 7.63 (s, 1H), 7.60 (s, 1H), 7.57-7.50 (m, 1H), 7.45-7.36(m, 1H), 6.95 (d, J=3.3 Hz, 1H), 6.29 (d, J=3.3 Hz, 1H), 5.26 and 5.24(each d, J=13.5 Hz, each 1H), 4.34 (sept, J=6.6 Hz, 1H), 2.42 (s, 3H),2.34 (s, 3H), 1.06 and 1.00 (each d, J=6.6 Hz, each 3H).

Example 5(34)4-[3-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]-3-methylbenzoicacid

TLC: Rf 0.50 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.88 (d, J=7.8 Hz, 1H), 7.86-7.74 (m, 4H), 7.59 (s, 1H),7.56-7.36 (m, 3H), 6.86 (d, J=3.3 Hz, 1H), 6.19 (d, J=3.3 Hz, 1H),5.40-4.90 (br, 2H), 3.47 (brd, J=6.9 Hz, 2H), 2.39 (s, 3H), 2.12 (s,3H), 1.65-1.50 (m, 1H), 0.83 (brd, J=6.3 Hz, 6H).

Example 5(35)4-[3-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]cinnamicacid

TLC: Rf 0.45 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.87 (d, J=7.8 Hz, 1H), 7.82 (d, J=7.8 Hz, 1H), 7.73 (d,J=8.4 Hz, 2H), 7.67-7.46 (m, 6H), 7.44-7.34 (m, 1H), 6.94 (d, J=3.3 Hz,1H), 6.56 (d, J=15.9 Hz, 1H), 6.28 (d, J=3.3 Hz, 1H), 5.27 and 5.21(each d, J=13.2 Hz, each 1H), 4.36 (sept, J=6.6 Hz, 1H), 2.33 (s, 3H),1.08 and 1.03 (each d, J=6.6 Hz, each 3H).

Example 5(36)4-[3-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]cinnamicacid

TLC: Rf 0.45 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.88 (d, J=8.4 Hz, 1H), 7.81 (s, 1H), 7.80 (d, J=8.1 Hz,1H), 7.72 (d, J=7.8 Hz, 2H), 7.61 (d, J=15.9 Hz, 1H), 7.55-7.34 (m, 2H),7.50 (s, 1H), 7.44 (d, J=7.8 Hz, 2H), 6.82 (d, J=3.6 Hz, 1H), 6.56 (d,J=15.9 Hz, 1H), 6.16 (d, J=3.6 Hz, 1H), 5.40-4.90 (br, 2H), 3.49 (d,J=6.6 Hz, 2H), 2.13 (s, 3H), 1.64-1.48 (m, 1H), 0.85 (d, J=6.6 Hz, 6H).

Example 5(37)4-[3-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]-3-methylcinnamicacid

TLC: Rf 0.46 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.87 (d, J=8.1 Hz, 1H), 7.86 (d, J=8.4 Hz, 1H),7.64-7.48 (m, 7H), 7.44-7.36 (m, 1H), 6.93 (d, J=3.6 Hz, 1H), 6.54 (d,J=15.9 Hz, 1H), 6.29 (d, J=3.6 Hz, 1H), 5.23 and 5.18 (each d, J=14.4Hz, each 1H), 4.33 (sept, J=6.6 Hz, 1H), 2.39 (s, 3H), 2.34 (s, 3H),1.06 and 1.00 (each d, J=6.6 Hz, each 3H).

Example 5(38)4-[3-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]-3-methylcinnamicacid

TLC: Rf 0.46 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.88 (d, J=8.1 Hz, 1H), 7.84 (d, J=8.4 Hz, 1H), 7.78 (s,1H), 7.62-7.47 (m, 5H), 7.44-7.35 (m, 2H), 6.84 (d, J=3.6 Hz, 1H), 6.54(d, J=16.2 Hz, 1H), 6.20 (d, J=3.6 Hz, 1H), 5.35-4.90 (br, 2H), 3.47 (d,J=7.2 Hz, 2H), 2.35 (s, 3H), 2.14 (s, 3H), 1.63-1.49 (m, 1H), 0.83 (d,J=6.3 Hz, 6H).

Example 5(39)4-[3-[N-isobutyl-N-[2-(4-methylthiazolyl)sulfonyl]amino]naphthalen-2-yloxymethyl]-3-methylcinnamicacid

TLC: Rf 0.71 (ethyl acetate:methanol=9:1);

NMR: δ 7.82-7.71 (m, 4H), 7.51-7.46 (m, 1H), 7.43-7.32 (m, 4H), 7.21 (s,1H), 6.95 (s, 1H), 6.48 (d, J=16.2 Hz, 1H), 5.04 and 4.91 (each br-m,total 2H), 3.83-3.60 (br-m, 2H), 2.38 (s, 3H), 2.34 (s, 3H), 1.81-1.67(m, 1H), 0.95 (br-s, 6H).

Example 5(40)4-[3-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]naphthalen-2-yloxymethyl]-3-methylbenzoicacid

TLC: Rf 0.71 (ethyl acetate:methanol=9:1);

NMR(DMSO-d₆): δ 7.88-7.83 (m, 2H), 7.65-7.47 (m, 8H), 7.42-7.37 (m, 1H),6.55 (d, J=15.9 Hz, 1H), 5.16 (s, 2H), 4.62-4.49 (m, 1H), 2.42 (s, 3H),2.36 (s, 3H), 1.13 (d, J=6.6 Hz, 3H), 1.03 (d, J=6.6 Hz, 3H).

Example 5(41)4-[6-[N-ethyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.34 (dichloromethane:methanol=19:1);

NMR: δ 8.10 (d, J=8.4 Hz, 2H), 7.35 (d, J=8.4 Hz, 2H), 7.14 (s, 1H),6.90 (brs, 1H), 6.79 (s, 1H), 4.92 (m, 2H), 4.20-3.60 (m, 2H), 2.90-2.83(m, 4H), 2.33 (s, 3H), 2.09 (m, 2H), 1.20 (t, J=7.2 Hz, 3H).

Example 5(42)4-[6-[N-(4-methyl-2-thiazolylsulfonyl)-N-propylamino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.34 (dichloromethane:methanol=19:1);

NMR: δ 8.11 (d, J=8.4 Hz, 2H), 7.35 (d, J=8.4 Hz, 2H), 7.15 (s, 1H),6.90 (brs, 1H), 6.78 (s, 1H), 5.10-4.70 (m, 2H), 4.00-3.50 (m, 2H),2.90-2.84 (m, 4H), 2.32 (s, 3H), 2.09 (m, 2H), 1.58 (m, 2H), 0.93 (t,J=7.5 Hz, 3H).

Example 5(43)4-[4,5-dimethyl-2-[N-(5-methyl-2-furylsulfonyl)-N-(2-propenyl)amino]phenoxymethyl]benzoicacid

TLC: Rf 0.44 (chloroform:methanol=9:1);

NMR: δ 8.12 (d, J=8.4 Hz, 2H), 7.43 (d, J=8.4 Hz, 2H), 7.01 (s, 1H),6.77 (d, J=3.0 Hz, 1H), 6.68 (s, 1H), 5.99-5.94 (m, 1H), 5.92-5.75 (m,1H), 5.16-5.03 (m, 2H), 5.02 (s, 2H), 4.42-4.20 (m, 2H), 2.21 (s, 3H),2.17 (s, 3H), 2.15 (s, 3H).

Example 5(44)4-[4,5-dimethyl-2-[N-methyl-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]-3-methylbenzoicacid

TLC: Rf 0.42 (chloroform:methanol=9:1);

NMR: δ 7.98-7.91 (m, 2H), 7.43 (d, J=8.7 Hz, 1H), 7.08 (s, 1H), 6.79 (d,J=3.3 Hz, 1H), 6.74 (s, 1H), 5.98 (m, 1H), 4.98 (s, 2H), 3.30 (s, 3H),2.38 (s, 3H), 2.24 (s, 3H), 2.19 (s, 3H), 2.15 (s, 3H).

Example 5(45)4-[4,5-dimethyl-2-[N-ethyl-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]-3-methylbenzoicacid

TLC: Rf 0.42 (chloroform:methanol=9:1);

NMR: δ 7.97-7.90 (m, 2H), 7.45 (d, J=8.1 Hz, 1H), 7.01 (s, 1H), 6.76 (s,1H), 6.75 (d, J=3.3 Hz, 1H), 5.95 (m, 1H), 4.96 (s, 2H), 3.82-3.66 (br,2H), 2.37 (s, 3H), 2.25 (s, 3H), 2.19 (s, 3H), 2.13 (s, 3H), 1.14 (t,J=7.2 Hz, 3H).

Example 5(46)4-[4,5-dimethyl-2-[N-(5-methyl-2-furylsulfonyl)-N-propylamino]phenoxymethyl]-3-methylbenzoicacid

TLC: Rf 0.42 (chloroform:methanol=9:1);

NMR: δ 7.98-7.90 (m, 2H), 7.45 (d, J=8.1 Hz, 1H), 7.02 (s, 1H),6.78-6.70 (m, 2H), 5.95 (m, 1H), 4.95 (s, 2H), 3.71-3.55 (br, 2H), 2.37(s, 3H), 2.24 (s, 3H), 2.19 (s, 3H), 2.12 (s, 3H), 1.60-1.44 (m, 2H),0.88 (t, J=7.5 Hz, 3H).

Example 5(47)4-[4,5-dimethyl-2-[N-(5-methyl-2-furylsulfonyl)-N-(2-propenyl)amino]phenoxymethyl]-3-methylbenzoicacid

TLC: Rf 0.45 (chloroform:methanol=9:1);

NMR: δ 7.98-7.90 (m, 2H), 7.45 (d, J=8.1 Hz, 1H), 7.01 (s, 1H), 6.77 (d,J=3.3 Hz, 1H), 6.71 (s, 1H), 5.96 (m, 1H), 5.83 (m, 1H), 5.15-5.00 (m,2H), 4.96 (s, 2H), 4.40-4.20 (br, 2H), 2.38 (s, 3H), 2.23 (s, 3H), 2.18(s, 3H), 2.14 (s, 3H).

Example 5(48)4-[4,5-dimethyl-2-[N-(2-hydroxy-2-methylpropyl)-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]-3-methylbenzoicacid

TLC: Rf 0.41 (chloroform:methanol=9:1);

NMR: δ 8.00-7.94 (m, 2H), 7.53 (d, J=7.8 Hz, 1H), 6.80 (s, 1H), 6.77 (s,1H), 6.75 (d, J=3.3 Hz, 1H), 6.01 (m, 1H), 5.08 (d, J=12.3 Hz, 1H), 5.00(d, J=12.3 Hz, 1H), 3.84 (d, J=14.4 Hz, 1H), 3.56 (d, J=14.4 Hz, 1H),2.42 (s, 3H), 2.23 (s, 3H), 2.21 (s, 3H), 2.14 (s, 3H), 1.25 (s, 3H),1.18 (s, 3H).

Example 5(49)4-[6-[N-methyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.34 (dichloromethane:methanol=19:1);

NMR: δ 8.11 (d, J=8.7 Hz, 2H), 7.35 (d, J=8.7 Hz, 2H), 7.20 (s, 1H),6.94 (brs, 1H), 6.78 (s, 1H), 4.92 (brs, 2H), 3.44 (s, 3H), 2.89-2.83(m, 4H), 2.35 (d, J=0.9 Hz, 3H), 2.08 (m, 2H).

Example 5(50)4-[6-[N-(2-hydroxy-2-methylpropyl)-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]-3-methylbenzoicacid

TLC: Rf 0.32 (chloroform:methanol=10:1);

NMR: 7.97 (d, J=7.8 Hz, 1H), 7.95 (s, 1H), 7.53 (d, J=7.8 Hz, 1H), 6.89(s, 1H), 6.86 (s, 1H), 6.75 (d, J=3.3 Hz, 1H), 6.01 (dd, J=3.3, 0.9 Hz,1H), 5.08 (d, J=12.9 Hz, 1H), 5.02 (d, J=12.9 Hz, 1H), 3.85 (d, J=14.7Hz, 1H), 3.58 (d, J=14.7 Hz, 1H), 2.90-2.78 (m, 4H), 2.42 (s, 3H), 2.21(s, 3H), 2.13-2.01 (m, 2H), 1.25 (s, 3H), 1.18 (s, 3H).

Example 5(51)3-methyl-4-[6-[N-methyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.45 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.60-7.50 (m, 3H), 7.49 (d, J=8.1 Hz, 1H), 7.20 (d,J=8.1 Hz, 1H), 7.09 (s, 1H), 7.04 (s, 1H), 6.53 (d, J=15.9 Hz, 1H), 4.87(br, 2H), 3.24 (s, 3H), 2.85 (t, J=7.4 Hz, 2H), 2.77 (t, J=7.4 Hz, 2H),2.25 (s, 3H), 2.23 (s, 3H), 2.10-1.95 (m, 2H).

Example 5(52)4-[6-[N-ethyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]-3-methylcinnamicacid

TLC: Rf 0.44 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.55 (d, J=16.0 Hz, 1H), 7.50-7.40 (m, 3H), 7.19 (d,J=8.1 Hz, 1H), 7.09 (s, 1H), 6.98 (s, 1H), 6.52 (d, J=16.0 Hz, 1H), 4.84(br, 2H), 3.66 (br, 2H), 2.85 (t, J=7.4 Hz, 2H), 2.77 (t, J=7.4 Hz, 2H),2.23 (s, 3H), 2.19 (s, 3H), 2.10-1.90 (m, 2H), 1.01 (t, J=7.0 Hz, 3H).

Example 5(53)4-[2-[N-cyclopropylmethyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid

TLC: Rf 0.41 (chloroform:methanol=9:1);

NMR: δ 8.11 (d, J=8.4 Hz, 2H), 7.43 (d, J=8.4 Hz, 2H), 7.09 (s, 1H),6.74 (d, J=3.0 Hz, 1H), 6.70 (s, 1H), 5.96-5.92 (m, 1H), 5.02 (brs, 2H),3.68-3.40 (m, 2H), 2.23 (s, 3H), 2.19 (s, 3H), 2.14 (s, 3H), 1.03-0.86(m, 1H), 0.46-0.35 (m, 2H), 0.21-0.06 (m, 2H).

Example 5(54)4-[4,5-dimethyl-2-[N-(2-hydroxy-2-methylpropyl)-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]benzoicacid

TLC: Rf 0.34 (chloroform:methanol=9:1);

NMR: δ 8.13 (d, J=8.4 Hz, 2H), 7.52 (d, J=8.4 Hz, 2H), 6.81 (s, 1H),6.75 (s, 1H), 6.74 (d, J=3.0 Hz, 1H), 6.03-5.98 (m, 1H), 5.22-4.96 (m,2H), 3.92-3.76 and 3.64-3.48 (each m, total 2H), 2.21 (s, 6H), 2.13 (s,3H), 1.28 and 1.19 (each brs, each 3H).

Example 5(55)3-methyl-4-[6-[N-(2-methyl-2-propenyl)-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.60 (chloroform:methanol=9:1);

NMR: δ 7.76 (d, J=15.9 Hz, 1H), 7.42-7.34 (m, 2H), 7.27-7.22 (m, 1H),7.12 (s, 1H), 6.92 (d, J=0.9 Hz, 1H), 6.78 (s, 1H), 6.47 (d, J=15.9 Hz,1H), 4.90-4.72 (m, 4H), 4.50-4.14 (m, 2H), 2.92-2.80 (m, 4H), 2.31 (s,6H), 2.18-2.00 (m, 2H), 1.81 (s, 3H).

Example 5(56)4-[6-[N-cyclopropylmethyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]-3-methylcinnamicacid

TLC: Rf 0.60 (chloroform:methanol=9:1);

NMR: δ 7.77 (d, J=15.9 Hz, 1H), 7.42-7.38 (m, 2H), 7.30-7.25 (m, 1H),7.21 (s, 1H), 6.89 (d, J=0.9 Hz, 1H), 6.82 (s, 1H), 6.46 (d, J=15.9 Hz,1H), 4.92-4.64 (m, 2H), 3.84-3.42 (m, 2H), 2.95-2.76 (m, 4H), 2.31 (s,3H), 2.31 (s, 3H), 2.18-2.02 (m, 2H), 1.08-0.90 (m, 1H), 0.46-0.40 (m,2H), 0.26-0.08 (m, 2H).

Example 5(57)4-[6-[N-(2-hydroxy-2-methylpropyl)-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.46 (chloroform:methanol=9:1);

NMR: δ 7.78 (d, J=15.9 Hz, 1H), 7.58 (d, J=8.1 Hz, 2H), 7.47 (d, J=8.1Hz, 2H), 6.85 (d, J=3.6 Hz, 2H), 6.74 (d, J=3.6 Hz, 1H), 6.47 (d, J=15.9Hz, 1H), 6.01 (d, J=2.1 Hz, 1H), 5.10 (d, J=12.0 Hz, 1H), 4.99 (d,J=12.0 Hz, 1H), 3.85 (d, J=14.1 Hz, 1H), 3.53 (d, J=14.1 Hz, 1H),2.90-2.77 (m, 4H), 2.23 (s, 3H), 2.07 (m, 2H), 1.27 (s, 3H), 1.16 (s,3H).

Example 5(58)3-methyl-4-[6-[N-(4-methyl-2-thiazolylsulfonyl)-N-(2-propenyl)amino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.42 (dichloromethane:methanol=10:1);

NMR: δ 7.76 (d, J=15.9 Hz, 1H), 7.42-7.36 (m, 2H), 7.28 (m, 1H), 7.11(s, 1H), 6.92 (m, 1H), 6.80 (s, 1H), 6.47 (d, J=15.9 Hz, 1H), 5.87 (m,1H), 5.11 (dd, J=17.1, 1.5 Hz, 1H), 5.07 (dd, J=8.7, 1.5 Hz, 1H), 4.83(br, 2H), 4.32 (br, 2H), 2.92-2.82 (m, 4H), 2.33 (d, J=0.6 Hz, 3H), 2.32(s, 3H), 2.16-2.04 (m, 2H).

Example 5(59)4-[6-[N-(2-hydroxy-2-methylpropyl)-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]-3-methylcinnamicacid

TLC: Rf 0.42 (dichloromethane:methanol=10:1);

NMR: δ 7.76 (d, J=15.9 Hz, 1H), 7.44-7.38 (m, 3H), 7.05 (m, 1H), 6.88(s, 1H), 6.82 (s, 1H), 6.46 (d, J=15.9 Hz, 1H), 5.03 (d, J=12.0 Hz, 1H),4.93 (d, J=12.0 Hz, 1H), 3.96 (d, J=14.4 Hz, 1H), 3.69 (d, J=14.4 Hz,1H), 2.87 (t, J=7.5 Hz, 2H), 2.77 (t, J=7.5 Hz, 2H), 2.43 (s, 3H), 2.40(s, 3H), 2.13-2.00 (m, 2H), 1.23 (s, 3H), 1.18 (s, 3H).

Example 5(60)4-[4,5-dimethyl-2-[N-cyclopropylmethyl-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]-3-methylbenzoicacid

TLC: Rf 0.45 (chloroform:methanol=9:1);

NMR: δ 8.00-7.92 (m, 2H), 7.47 (d, J=7.8 Hz, 1H), 7.09 (s, 1H),6.78-6.71 (m, 2H), 5.94 (m, 1H), 4.96 (s, 2H), 3.63-3.45 (br, 2H), 2.37(s, 3H), 2.25 (s, 3H), 2.19 (s, 3H), 2.13 (s, 3H), 0.95 (m, 1H),0.44-0.35 (m, 2H), 0.15-0.22 (m, 2H).

Example 5(61)3-methyl-4-[6-[N-(4-methyl-2-thiazolylsulfonyl)-N-propylamino]indan-5-yloxymethyl]cinnamicacid

TLC: Rf 0.41 (chloroform:methanol=9:1);

NMR: δ 7.76 (d, J=16.2 Hz, 1H), 7.44-7.34 (m, 2H), 7.32-7.20 (m, 1H),7.13 (s, 1H), 6.90 (s, 1H), 6.82 (s, 1H), 6.46 (d, J=16.2 Hz, 1H),4.90-4.70 (m, 2H), 3.90-3.50 (m, 2H), 2.89 (t, J=7.5 Hz) and 2.86 (t,J=7.5 Hz) total 4H, 2.31 (s) and 2.30 (s) total 6H, 2.09 (quint, J=7.5Hz, 2H), 1.58 (m, 2H), 0.91 (t, J=7.5 Hz, 3H).

Example 5(62)4-[6-[N-(2-hydroxy-2-methylpropyl)-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid

TLC: Rf 0.29 (dichloromethane:methanol=19:1);

NMR: δ 8.13 (d, J=7.8 Hz, 2H), 7.48 (d, J=7.8 Hz, 2H), 7.02 (brs, 1H),6.90 (s, 1H), 6.83 (s, 1H), 5.12 (d, J=12.6 Hz, 1H), 4.95 (d, J=12.6 Hz,1H), 3.96 (d, J=15.0 Hz, 1H), 3.77 (d, J=15.0 Hz, 1H), 2.88-2.75 (m,4H), 2.42 (s, 3H), 2.06 (m, 2H), 1.29 (s, 3H), 1.22 (s, 3H).

Example 63-methyl-4-[6-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid sodium salt

To a suspension of the compound prepared in Example 2(74) (213 g) inethanol (2 L), 5N aqueous solution of sodium hydroxide (74.7 ml) wasadded and the mixture was stirred for 0.5 hour at 80° C. The reactionsolution was filtered under heating to remove the insolubles, then themixture was cooled, and the precipitate was collected. The mother liquorwas concentrated and the residue was dissolved in ethanol (500 ml) andwater (25 ml) under heating. The mixture was filtered under heating toremove the insolubles, then the mixture was cooled, and the precipitatewas collected. Under heating, all collected solids were dried underreduced pressure to give the compound of the present invention (165 g)having the following physical data.

TLC: Rf 0.52 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.49 (s, 1H), 7.29 (s, 1H), 7.26 (d, J=8.1 Hz, 1H),7.10-7.00 (m, 4H), 6.38 (d, J=15.9 Hz, 1H), 4.89 (br-d, J=10.5 Hz, 1H),4.63 (br-d, J=10.5 Hz, 1H), 3.55-3.25 (m, 2H), 2.85 (t, J=7.2 Hz, 2H),2.78 (t, J=7.2 Hz, 2H), 2.21 (s, 3H), 2.18 (s, 3H), 2.10-1.90 (m, 2H),1.60-1.45 (m, 1H), 1.00-0.70 (m, 6H).

Example 6(1)4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoicacid sodium salt

TLC: Rf 0.50 (chloroform:methanol=9:1);

NMR: δ 7.84 (d, J=8.1 Hz, 2H), 7.20-6.95 (m, 5H), 6.65 (d, J=3.3 Hz,1H), 5.84 (d, J=3.3 Hz, 1H), 4.75 (brs, 2H), 4.30-4.10 (m, 1H), 2.12 (s,3H), 0.86 (brd, J=3.9 Hz, 6H).

Example 6(2)4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid sodium salt

TLC: Rf 0.40 (chloroform:methanol=9:1);

NMR: δ 7.83 (d, J=8.1 Hz, 2H), 7.00 (d, J=8.1 Hz, 2H), 6.88 (s, 1H),6.59 (s, 1H), 6.54 (d, J=3.0 Hz, 1H), 5.74 (s, 1H), 4.90-4.50 (m, 2H),3.33 (brd, J=6.3 Hz, 2H), 2.09 (s, 3H), 2.05 (s, 3H), 1.93 (s, 3H),1.60-1.40 (m, 1H), 0.73 (d, J=6.3 Hz, 6H).

Example 6(3)3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid sodium salt

TLC: Rf 0.41 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.70 (s, 1H), 7.66 (d, J=7.8 Hz, 1H), 7.13 (d, J=7.8 Hz,1H), 6.99 (s, 1H), 6.91 (s, 1H), 6.76 (d, J=3.3 Hz, 1H), 6.14 (d, J=3.3Hz, 1H), 4.88 (brs, 2H), 3.36 (d, J=6.9 Hz, 2H), 2.26 (s, 3H), 2.22 (s,3H), 2.14 (s, 3H), 2.10 (s, 3H), 1.60-1.45 (m, 1H), 0.81 (brd, J=6.3 Hz,6H).

Example 6(4)4-[6-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid sodium salt

TLC: Rf 0.40 (chloroform:methanol=9:1);

NMR(CD₃OD): δ 7.91 (d, J=8.1 Hz, 2H), 7.19 (s, 1H), 7.18 (d, J=8.1 Hz,2H), 7.13 (s, 1H), 6.93 (s, 1H), 5.00-4.80 (m, 1H), 4.65-4.58 (m, 1H),3.65-3.48 (m, 2H), 2.95-2.80 (m, 4H), 2.21 (d, J=0.9 Hz, 3H), 2.09(quint, J=7.5 Hz, 2H), 1.66 (m, 1H), 1.03-0.85 (m, 6H).

Example 6(5)4-[6-[N-isobutyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid potassium salt

TLC: Rf 0.37 (chloroform:methanol=9:1);

NMR(DMSO-d₆): δ 7.81 (d, J=8.0 Hz, 2H), 7.47 (q, J=0.4 Hz, 1H), 7.06 (d,J=8.0 Hz, 1H), 7.03 (s, 2H), 6.95 (s, 1H), 5.10-4.80 (m, 1H), 4.80-4.50(m, 1H), 3.43 (brs, 2H), 2.80 (q, J=7.0 Hz, 4H), 2.23 (d, J=0.4 Hz, 3H),2.01 (qn, J=7.0 Hz, 2H), 1.53 (sept, J=6.6 Hz, 1H), 0.85 (brs, 6H).

Example 6(6)4-[6-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid sodium salt

TLC: Rf 0.51 (chloroform:methanol=9:1);

NMR: δ 7.37 (d, J=15.9 Hz, 1H), 7.17 (d, J=7.5 Hz, 2H), 7.10-6.90 (m,3H), 6.67 (s, 1H), 6.55 (s, 1H), 6.45 (d, J=15.9 Hz, 1H), 5.74 (s, 1H),4.80-4.45 (m, 2H), 3.35 (d, J=6.3 Hz, 2H), 2.85-2.55 (m, 4H), 2.10-1.80(m, 5H), 1.65-1.40 (m, 1H), 0.74 (brs, 6H).

Example 6(7)3-methyl-4-[6-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid sodium salt

TLC: Rf 0.60 (chloroform:methanol=9:1);

NMR(CD₃OD): δ 7.78 (s) and 7.75 (d, J=8.1 Hz) total 2H, 7.24 (d, J=8.1Hz, 1H), 7.07 (s, 1H), 6.97 (s, 1H), 6.64 (d, J=3.3 Hz, 1H), 6.03 (dd,J=3.3, 0.9 Hz, 1H), 5.08-4.75 (m, 2H), 3.48 (d, J=7.5 Hz, 2H), 2.94-2.80(m, 4H), 2.32 (s, 3H), 2.15-2.00 (m) and 2.04 (s) total 5H, 1.87 (m,1H), 0.98-0.80 (m, 6H).

Example 6(8)4-[6-[N-isopropyl-N-(4-methyl-2-thiazolylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid potassium salt

TLC: Rf 0.36 (chloroform:methanol=9:1);

NMR: δ 7.27 (d, J=15.9 Hz, 1H), 7.21 (d, J=7.5 Hz, 2H), 6.98 (d, J=7.5Hz, 2H), 6.84 (s, 1H), 6.78 (s, 1H), 6.70 (s, 1H), 6.41 (d, J=15.9 Hz,1H), 4.70-4.40 (m, 3H), 2.85-2.60 (m, 4H), 2.24 (s, 3H), 2.05-1.90 (m,2H), 1.01 (d, J=6.6 Hz, 3H), 0.95 (d, J=6.6 Hz, 3H).

Example 6(9)4-[2-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid potassium salt

TLC: Rf 0.32 (chloroform:methanol=9:1);

NMR: δ 7.82 (d, J=8.1 Hz, 2H), 7.33 (d, J=3.0 Hz, 1H), 7.15 (d, J=3.0Hz, 1H), 6.94 (s, 1H), 6.89 (d, J=8.1 Hz, 2H), 6.56 (s, 1H), 4.70-4.55(m, 1H), 4.45-4.25 (m, 1H), 3.60-3.30 (m, 2H), 2.09 (s, 6H), 1.60-1.45(m, 1H), 0.78 (brs, 3H), 0.72 (brs, 3H).

Example 6(10)3-methyl-4-[2-[N-isobutyl-N-(2-thiazolylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid sodium salt

TLC: Rf 0.37 (chloroform:methanol=10:1);

NMR(DMSO-d₆): δ 7.98 (d, J=3.0 Hz, 1H), 7.82 (d, J=3.0 Hz, 1H), 7.64 (s,1H), 7.60 (d, J=7.8 Hz, 1H), 6.99 (d, J=7.8 Hz, 1H), 6.97 (s, 1H), 6.91(s, 1H), 5.00-4.54 (m, 2H), 3.42 (d, J=6.3 Hz, 2H), 2.20 (s, 3H), 2.20(s, 3H), 2.11 (s, 3H), 1.50 (m, 1H), 0.90-0.73 (m, 6H).

Example 74-[6-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]-3-methylbenzylalcohol

To a suspension of the compound prepared in Example 2(33) (1.20 g) intetrahydrofuran (10 ml), borohydride-dimethylthiol complex (2Mtetrahydrofuran solution, 6.0 ml) was added and the mixture was stirredfor 1 hour. To the reaction mixture, methanol, water and 1N hydrochloricacid were added, and was extracted with ethyl acetate twice. Thecombined organic layer was washed with 1N hydrochloric acid, water and asaturated aqueous solution of sodium chloride successively, dried overan anhydrous sodium sulfate and was purified by column chromatography onsilica gel (n-hexane:ethyl acetate=from 8:1 to 2:1) to give the compoundof the present invention (947 mg) having the following physical data.

TLC: Rf 0.57 (n-hexane:ethyl acetate=1:1);

NMR: δ 7.20 (d, J=7.8 Hz, 1H), 7.13 (s, 1H), 7.10 (d, J=7.8 Hz, 1H),7.07 (s, 1H), 6.95 (s, 1H), 6.79 (d, J=3.3 Hz, 1H), 6.20-6.15 (m, 1H),4.94 (br, 1H), 4.83 (br, 1H), 4.45 (s, 2H), 3.32 (d, J=6.9 Hz, 2H), 2.84(t, J=7.4 Hz, 2H), 2.78 (t, J=7.4 Hz, 2H), 2.25 (s, 3H), 2.13 (s, 3H),2.10-1.90 (m, 2H), 1.55-1.40 (m, 1H), 0.90-0.70 (m, 6H).

Reference Example 5 Methyl t-butyl ether solution of4-methyl-2-thiazolylsulfonylchloride

Under atmosphere of argon, to a solution of 4-methylthiazole (3.0 g) inmethyl t-butyl ether (45 ml), n-butyl lithium (1.58 M hexane solution,19.1 ml) was added under stirring at −78° C., and the mixture wasstirred for 1 hour. 5.72M solution of sulfur dioxide in tetrahydrofuran(5.3 ml) was added dropwise to the mixture, and the mixture was stirredfor 1 hour. To the mixture, N-chlorosuccinimide (4.44 g) was added. Thenthe mixture was warmed to 0° C. and stirred for another 1 hour. Waterwas added to the reaction mixture, and the organic layer was washed withwater twice, with a saturated aqueous solution of sodium chloride once,and was dried over an anhydrous magnesium sulfate to give the titlecompound, as methyl t-butyl ether solution (92 ml). The concentration ofthis solution was 0.20 M. The conversion yield of the title compound was3.69 g.

Example 8 1-(4-methylthiazol-2-ylsulfonyloxy)-1,2,3-benzotriazole

Under atmosphere of argon, to a solution of 4-methylthiazol-2-sulfonylchloride in methyl t-butyl ether (0.20 M, 20 ml), 1-hydroxybenzotriazole(549 mg) and triethylamine (0.57 ml) were added under stirring withcooled on ice bath, and the mixture was stirred for 1 hour at roomtemperature. To the reaction mixture, ethyl acetate was added. Theorganic layer was washed with water three times, with a saturatedaqueous solution of sodium chloride once successively, dried over ananhydrous magnesium sulfate and concentrated to give the compound of thepresent invention (1.1 g) having the following physical data.

NMR: δ 8.03 (dt, J=8.4, 1.0 Hz, 1H), 7.70-6.57 (m, 2H), 7.53 (d, J=1.0Hz, 1H), 7.46 (ddd, J=8.4, 5.8, 2.0 Hz, 1H), 2.62 (d, J=1.0 Hz, 3H).

Example 9 1-(4-methylthiazol-2-ylsulfonyl)-3-methylimidazol-1-oniumhydrogen chloride salt

Under atmosphere of argon, a solution of 4-methylthiazol-2-sulfonylchloride in methyl t-butyl ether (0.14 M, 30 ml) was cooled to 0° C.,then 1-methylimidazole (0.68 ml) was added and the mixture was stirredfor 1 hour. The white precipitate appeared was collected and dried togive the compound of the present invention (1.56 g) having the followingphysical data.

NMR(DMSO-d₆): δ 9.08 (brs, 1H), 7.69 (t, J=1.8 Hz, 1H), 7.63 (t, J=1.8Hz, 1H), 7.20-7.17 (m, 1H), 3.96 (s, 3H), 2.31 (d, J=1.8 Hz, 3H).

Among the compounds of formula (I) of the present invention, thecompounds wherein Ar is thiazole (prepared in Examples 2(36) to (74),(101) to (123), Examples 3(6) to (20), Examples 4(7) to (17), Examples5(5) to (10), (22) to (27), (31) to (33), (40) to (43), (50), (52),(53), (56), (57), (59), (60), (62), (63), Example 6, Examples 6(4), (5),(8) to (10)), the compounds wherein Ar is pyridine (prepared in Examples2(75) to (97), Examples 3(21) to (38), Examples 4(18) to (22)) may beprepared by the same procedures of Reference Example 3 using thecompound prepared in Examples 8 and 9 or a corresponding compound inplace of a corresponding sulfonyl chloride, followed by correspondingprocedures.

Comparison Example 1 A Comparison of the Stability of4-methyl-2-thiazolylsulfonyl chloride with that of the Compound Preparedin Examples 8 and 9

The solution prepared in Reference Example 1 was concentrated underreduced pressure to give 4-methyl-2-thiazolylsulfonyl chloride. Thestability of this compound and the compounds prepared in Examples 8 and9 was measured on HPLC. The conditions of HPLC were as follows.

Column: YMC-Pack ODS-AM-302(4.6 mm*150 mm)

Eluting solvent: MeCN/3 mM tetra-n-butylammonium phosphate=40/60

Flow rate: 1 ml/min

Detected by UVabs 220 nm

The results are shown in table 4.

TABLE 4 Temperature Residual Compounds (° C.) Time (hour) Rate (%)4-methyl-2-thiazolylsulfonyl 1 24 102.0 chloride 1 48 96.3 1 72 98.6 2024 71.4 20 48 20.6 20 66 2.0 40 16 60.9 40 24 7.6 Compound prepared inex. 8 40 24 99.8 Compound prepared in ex. 9 40 24 99.6

Table 4 shows that 4-methyl-2-thiazolylsulfonyl chloride is stable atlow temperature, but when subjected to room temperature or higher, it ishard to assure the stability.

On the other hand, the compounds prepared in Examples 8 and 9 are stableeven at high temperature, since the residual rate thereof hardly changedwhen they were left at 40° C. for one day.

Therefore, the compound of formula (II), given in the present invention,is useful as an intermediate for a sulfonamide compound, since itsstability is improved compared with the corresponding sulfonyl halidecompound.

Formulation Example 1

The following compounds were admixed in conventional method and punchedout to obtain 100 tablets each containing 5 mg of active ingredient.

3-Methyl-4-[2-[N-isobutyl-N-(5-methyl-2- 500 mgfurylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoic acid Cellulosecalcium glycolate (disintegrant) 200 mg Magnesium stearate (lubricant)100 mg Microcrystalline cellulose 9.2 g

Formulation Example 2

The following compounds were admixed in conventional method and solutionis sterilized, filled into vials each containing 1 ml and lyophilized toobtain 100 vials each containing 5 mg of active ingredient.

3-Methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]- 500 mg4,5-dimethylphenoxymethyl]benzoic acid Mannit  50 g Distilled water 100ml

1. An N-phenylarylsulfonylamide compound of formula (I):

wherein R¹ is COOH, 5-tetrazolyl, 5-oxo-1,2,4-oxadiazolyl, CH₂OH or5-oxo-1,2,4-thiadiazolyl; R² is hydrogen, methyl, methoxy or chloro; R³and R⁴ are a combination of (1) methyl and methyl, (2) methyl andchloro, (3) chloro and methyl, or (4) trifluoromethyl and hydrogen; orR³ and R⁴ are taken together with the carbon to which R³ and R⁴ areattached to form (5) cyclopentene, (6) cyclohexene or (7) benzene ring;R⁵ is isopropyl, isobutyl, 2-methyl-2-propenyl, cyclopropylmethyl,methyl, ethyl, propyl, 2-propenyl or 2-hydroxy-2-methylpropyl; Ar ispyridyl or 5-methyl-2-furyl; and n is zero or 1, and when R¹ is5-tetrazolyl, 5-oxo-1,2,4-oxadiazolyl or 5-oxo-1,2,4-thiadiazolyl, n iszero, an alkyl ester thereof or a non-toxic salt thereof.
 2. Thecompound according to claim 1, wherein Ar is 5-methyl-2-furyl, 2-pyridylor 3-pyridyl.
 3. The compound according to claim 1, wherein Ar is5-methyl-2-furyl.
 4. The compound according to claim 1, which isselected from the group consisting of (1)4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamicacid, (2)4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoicacid, (3)4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoicacid, (4)4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid, (5)4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid, (6)4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid, (7)3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid, (8)3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid, (9)3-chloro-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid, (10)3-chloro-4-[2-[N-isopropyl-N-(5-ethyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid, (11)3-methoxy-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid, (12)3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid, (13)3-methoxy-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid, (14)3-methoxy-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid, (15)3-methoxy-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid, (16)3-chloro-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]-benzoicacid, (17)3-chloro-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid, (18)3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]cinnamicacid, (19)4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamicacid, (20)4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamicacid, (21)4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid, (22)3-methyl-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamicacid, (23)3-methyl-4-[2[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid, (24)3-methyl-4-[2-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid, (25)3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid, (26)4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid, (27)N-[4-chloro-5-methyl-2-[2-methyl-4-(5-tetrazoyl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide,(28)3-methoxy-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamicacid, (29)N-[4,5-dimethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide,(30)N-[4,5-dimethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(5-methyl-2-furyl)sulfonylamide,(31)N-[4-chloro-5-methyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide,(32)N-[4-chloro-5-methyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-(5-methyl-2-furyl)sulfonylamide,(33)N-[4-chloro-5-methyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide,(34)4-[6-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid, (35)4-[6-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid, (36)4-[7-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-1,2,3,4-tetrahydronaphthalen-6-yloxymethyl]benzoicacid, (37)4-[7-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]-1,2,3,4-tetrahydronaphthalen-6-yloxymethyl]benzoicacid, (38)N-[4,5-dimethyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-(5-methyl-2-furyl)sulfonylamide,(39)N-[4,5-dimethyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide,(40)N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-(5-methyl-2-furyl)sulfonylamide,(41)N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide,(42)N-[4,5-dimethyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide,(43)3-methyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamicacid, (44)N-[4,5-dimethyl-2-[2-methoxy-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-(5-methyl-2-furyl)sulfonylamide,(45)N-[4,5-dimethyl-2-[2-methoxy-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-(5-methyl-2-furyl)sulfonylamide,(46)4-[6-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid, (47)3-methyl-4-[6-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid, (48)3-methyl-4-[6-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid, (49)4-[2-[N-(2-methyl-2-propenyl)-N-(5-methyl-2-furylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid, (50)3-methyl-4-[6-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid, (51)3-methyl-4-[6-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid, (52)4-[6-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid, (53)4-[3-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-2-naphthyloxymethyl]benzoicacid, (54)3,5-dimethyl-4-[2-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoicacid, (55)3-methyl-4-[6-[N-(2-methyl-2-propenyl)-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid, (56)4-[6-[N-cyclopropylmethyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]-3-methylbenzoicacid, (57)4-[6-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]-3-methylbenzylalcohol,(58)3-methyl-4-[6-[N-methyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid, (59)4-[6-[N-ethyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]-3-methylbenzoicacid, (60)4-[[N-methyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacids (61)4-[6-[N-ethyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid, (62)4-[6-[N-propyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid, (63)4-[4,5-dimethyl-2-[(2-methyl-2-propenyl)-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]-3-methylbenzoicacid, (64)4-[6-[N-(2-methyl-2-propenyl)-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxy-methyl]cinnamicacid, (65)4-[6-[N-cyclopropylmethyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid, (66)4-[6-[N-(2-propenyl)-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid, (67)3-methyl-4-[b-[N-propyl-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid, (68)3-methyl-4-[6-[N-(2-propenyl)-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]benzoicacid, (69)4-[4,5-dimethyl-2-[N-methyl-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]benzoicacid, (70)4-[4,5-dimethyl-2-[N-ethyl-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]benzoicacid, (71)4-[4,5-dimethyl-2-[N-(5-methyl-2-furylsulfonyl)-N-propylamino]phenoxymethyl]benzoicacid, (72)4-[3-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]-3-methylbenzoicacid, (73)4-[3-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]-3-methylbenzoicacid, (74)4-[3-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]cinnamicacid, (75)4-[3-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]cinnamicacid, (76)3-methyl-4-[3-[N-isopropyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]cinnamicacid, (77)3-methyl-4-[3-[N-isobutyl-N-(5-methyl-2-furylsulfonyl)amino]naphthalen-2-yloxymethyl]cinnamicacid, (78)4-[4,5-dimethyl-2-[N-[(5-methyl-2-furyl)sulfonyl]-N-2-propenylamino]phenoxymethyl]benzoicacid, (79)4-[4,5-dimethyl-2-[N-methyl-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]-3-methylbenzoicacid, (80)4-[4,5-dimethyl-2-[N-ethyl-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]-3-methylbenzoicacid, (81)4-[4,5-dimethyl-2-[N-(5-methyl-2-furylsulfonyl)-N-propylamino]phenoxymethyl]-3-methylbenzoicacid, (82)4-[4,5-dimethyl-2-[N-(5-methyl-2-furylsulfonyl)-N-(2-propenyl)amino]phenoxymethyl]-3-methylbenzoicacid, (83)4-[4,5-dimethyl-2-[N-(2-hydroxy-2-methylpropyl)-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]-3-methylbenzoicacid, (84)4-[6-[N-(2-hydroxy-2-methylpropyl)-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]-3-methylbenzoicacid, (85)4-[4,5-dimethyl-2-[N-cyclopropylmethyl-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]benzoicacid, (86)4-[4,5-dimethyl-2-[N-(2-hydroxy-2-methylpropyl)-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]benzoicacid, (87)4-[6-[N-(2-hydroxy-2-methylpropyl)-N-(5-methyl-2-furylsulfonyl)amino]indan-5-yloxymethyl]cinnamicacid, and (88)4-[4,5-dimethyl-2-[N-cyclopropylmethyl-N-(5-methyl-2-furylsulfonyl)amino]phenoxymethyl]-3-methylbenzoicacid.
 5. The compound according to claim 1, wherein Ar is 2-pyridyl or3-pyridyl.
 6. The compound according to claim 1, which is selected fromthe group consisting of (1)4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamic(2)4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]benzoicacid, (3)3-chloro-4-[2-[N-isopropyl-N-(2-pyridylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid, (4)3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid, (5)3-methyl-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]benzoicacid, (6)3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid, (7)N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-3-pyridylsulfonylamide,(8)N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide,(9)4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid, (10)3-chloro-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid, (11)3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamicacid, (12)3-methoxy-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid, (13)3-methoxy-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid, (14)3-methyl-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid, (15)3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid, (16)N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide,(17)N-[4-trifluoromethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide,(18)3-methyl-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]benzoicacid, (19)4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]benzoicacid, (20)N-[4-trifluoromethyl-2-[4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide,(21)4-[2-[N-isopropyl-N-(2-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamicacid, (22)3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4-methyl-5-chlorophenoxymethyl]cinnamicacid, (23)3-methyl-4-[2-[N-isobutyl-N-(2-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid, (24)4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid, (25)3-methyl-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid, (26)N-[4-difluoromethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide,(27)3-chloro-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4,5-dimethylphenoxymethyl]cinnamicacid, (28)N-[4,5-dimethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide,(29)N-[4,5-dimethyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide,(30)N-[4-chloro-5-methyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide,(31)N-[4,5-dimethyl-2-[2-chloro-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide,(32)N-[4,5-dimethyl-2-[2-chloro-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-3-pyridylsulfonylamide,(33)N-[4,5-dimethyl-2-[2-chloro-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide,(34)3-methyl-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-4-chloro-5-methylphenoxymethyl]cinnamicacid, (35)N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide,(36)N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide,(37)N-[4,5-dimethyl-2-[4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide,(38)3-chloro-4-[2-[N-isobutyl-N-(3-pyridylsulfonyl)amino]-5-trifluoromethylphenoxymethyl]cinnamicacid, (39)N-[4-chloro-5-methyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide,(40)N-[4-chloro-5-methyl-2-[2-methyl-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide,(41)N-[4,5-dimethyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide,(42)N-[4,5-dimethyl-2-[2-methyl-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-3-pyridylsulfonylamide,(43)N-[4,5-dimethyl-2-[2-methoxy-4-(5-tetrazolyl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide,(44)N-(4,5-dimethyl-2-[2-methoxy-4-(5-tetrazolyl)phenylmethyloxy]phenyl)-N-isopropyl-2-pyridylsulfonylamide,(45)N-[4,5-dimethyl-2-[2-methoxy-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isobutyl-2-pyridylsulfonylamide,and (46)N-[4,5-dimethyl-2-[2-methoxy-4-(5-oxo-1,2,4-oxadiazol-3-yl)phenylmethyloxy]phenyl]-N-isopropyl-2-pyridylsulfonylamide.7. An antagonist of EP1 receptor which is a prostaglandin E2 receptorsubtype, comprising the N-phenylarylsulfonylamide compound of formula(I):

wherein R¹ is COOH, 5-tetrazolyl, 5-oxo-1,2,4-oxadiazolyl, CH₂OH or5-oxo-1,2,4-thiadiazolyl; R² is hydrogen, methyl, methoxy or chloro; R³and R⁴ are a combination of (1) methyl and methyl, (2) methyl andchloro, (3) chloro and methyl, or (4) trifluoromethyl and hydrogen; orR³ and R⁴ are taken together with the carbon to which R³ and R⁴ areattached to form (5) cyclopentene, (6) cyclohexene or (7) benzene ring;R⁵ is isopropyl, isobutyl, 2-methyl-2-propenyl, cyclopropylmethyl,methyl, ethyl, propyl, 2-propenyl or 2-hydroxy-2-methylpropyl; Ar ispyridyl or 5-methyl-2-furyl; and n is zero or 1, and when R¹ is5-tetrazolyl, 5-oxo-1,2,4-oxadiazolyl or 5-oxo-1,2,4-thiadiazolyl, n iszero, an ester thereof or a non-toxic salt thereof as an activeingredient.
 8. A pharmaceutical composition, which comprises theN-phenylarylsulfonylamide compound of formula (I):

wherein R¹ is COOH, 5-tetrazolyl, 5-oxo-1,2,4-oxadiazolyl, CH₂OH or5-oxo-1,2,4-thiadiazolyl; R² is hydrogen, methyl, methoxy or chloro; R³and R⁴ are a combination of (1) methyl and methyl, (2) methyl andchloro, (3) chloro and methyl, or (4) trifluoromethyl and hydrogen; orR³ and R⁴ are taken together with the carbon to which R³ and R⁴ areattached to form (5) cyclopentene, (6) cyclohexene or (7) benzene ring;R⁵ is isopropyl, isobutyl, 2-methyl-2-propenyl, cyclopropylmethyl,methyl, ethyl, propyl, 2-propenyl or 2-hydroxy-2-methylpropyl; Ar ispyridyl or 5-methyl-2-furyl; and n is zero or 1, and when R¹ is5-tetrazolyl, 5-oxo-1,2,4-oxadiazolyl or 5-oxo-1,2,4-thiadiazolyl, n iszero, an ester thereof or a non-toxic salt thereof as an activeingredient.
 9. A method for treating a disease, which comprisesadministering to a subject in need thereof the N-phenylarylsulfonylamidecompound of formula (I):

wherein R¹ is COOH, 5-tetrazolyl, 5-oxo-1,2,4-oxadiazolyl, CH₂OH or5-oxo-1,2,4-thiadiazolyl; R² is hydrogen, methyl, methoxy or chloro; R³and R⁴ are a combination of (1) methyl and methyl, (2) methyl andchloro, (3) chloro and methyl, or (4) trifluoromethyl and hydrogen; orR³ and R⁴ are taken together with the carbon to which R³ and R⁴ areattached to form (5) cyclopentene, (6) cyclohexene or (7) benzene ring;R⁵ is isopropyl, isobutyl, 2-methyl-2-propenyl, cyclopropylmethyl,methyl, ethyl, propyl, 2-propenyl or 2-hydroxy-2-methylpropyl; Ar ispyridyl or 5-methyl-2-furyl; and n is zero or 1, and when R¹ is5-tetrazolyl, 5-oxo-1,2,4-oxadiazolyl or 5-oxo-1,2,4-thiadiazolyl, n iszero, an ester thereof or a non-toxic salt thereof as an activeingredient, wherein the disease is pollakiuria or acraturesis.